Next Issue
Previous Issue

Table of Contents

Cells, Volume 1, Issue 3 (September 2012), Pages 204-666

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-22
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Optimal Thawing of Cryopreserved Peripheral Blood Mononuclear Cells for Use in High-Throughput Human Immune Monitoring Studies
Cells 2012, 1(3), 313-324; doi:10.3390/cells1030313
Received: 7 May 2012 / Revised: 29 June 2012 / Accepted: 3 July 2012 / Published: 25 July 2012
Cited by 16 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
Cryopreserved peripheral blood mononuclear cells (PBMC) constitute an important component of immune monitoring studies as they allow for efficient batch- testing of samples as well as for the validation and extension of original studies in the future. In this study, we systematically test
[...] Read more.
Cryopreserved peripheral blood mononuclear cells (PBMC) constitute an important component of immune monitoring studies as they allow for efficient batch- testing of samples as well as for the validation and extension of original studies in the future. In this study, we systematically test the permutations of PBMC thawing practices commonly employed in the field and identify conditions that are high and low risk for the viability of PBMC and their functionality in downstream ELISPOT assays. The study identifies the addition of ice-chilled washing media to thawed cells at the same temperature as being a high risk practice, as it yields significantly lower viability and functionality of recovered PBMC when compared to warming the cryovials to 37 °C and adding a warm washing medium. We found thawed PBMC in cryovials could be kept up to 30 minutes at 37 °C in the presence of DMSO before commencement of washing, which surprisingly identifies exposure to DMSO as a low risk step during the thawing process. This latter finding is of considerable practical relevance since it permits batch-thawing of PBMC in high-throughput immune monitoring environments. Full article
Open AccessArticle Resting of Cryopreserved PBMC Does Not Generally Benefit the Performance of Antigen-Specific T Cell ELISPOT Assays
Cells 2012, 1(3), 409-427; doi:10.3390/cells1030409
Received: 13 June 2012 / Revised: 12 July 2012 / Accepted: 14 July 2012 / Published: 30 July 2012
Cited by 9 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text
Abstract
T cell monitoring is increasingly performed using cryopreserved PBMC. It has been suggested that resting of PBMC after thawing, that is, culturing them overnight in test medium, produces higher antigen-induced spot counts in ELISPOT assays. To evaluate the importance of overnight resting, we
[...] Read more.
T cell monitoring is increasingly performed using cryopreserved PBMC. It has been suggested that resting of PBMC after thawing, that is, culturing them overnight in test medium, produces higher antigen-induced spot counts in ELISPOT assays. To evaluate the importance of overnight resting, we systematically tested cryopreserved PBMC from 25 healthy donors. CEF peptides (comprising CMV, EBV and flu antigens) were used to stimulate CD8 cells and mumps antigen to stimulate CD4 cells. The data show that resting significantly increased antigen-elicited T cell responses only for CEF high responder PBMC. The maximal gain observed was doubling of spot counts. For CEF low responders, and for mumps responders of either low- or high reactivity levels, resting had no statistically significant effect on the observed spot counts. Therefore, resting is not a generally applicable approach to improve ELISPOT assay performance, but can be recommended only for clinical subject cohorts and antigens for which it has a proven benefit. Because resting invariably leads to losing about half of the PBMC available for testing, and because doubling the PBMC numbers plated into the assay reliably doubles the antigen-induced spot counts, we suggest the latter approach as a simple and reliable alternative to resting for enhancing the performance of ELISPOT assays. Our data imply that resting is not required if PBMC were cryopreserved and thawed under conditions that minimize apoptosis of the cells. Therefore, this study should draw attention to the need to optimize freezing and thawing conditions for successful T cell work. Full article
(This article belongs to the Special Issue ELISPOT Research)
Open AccessArticle Neuroantigen-Specific CD4 Cells Expressing Interferon-γ (IFN-γ), Interleukin (IL)-2 and IL-3 in a Mutually Exclusive Manner Prevail in Experimental Allergic Encephalomyelitis (EAE)
Cells 2012, 1(3), 576-596; doi:10.3390/cells1030576
Received: 16 July 2012 / Revised: 28 July 2012 / Accepted: 31 July 2012 / Published: 24 August 2012
Cited by 1 | PDF Full-text (591 KB) | HTML Full-text | XML Full-text
Abstract
Experimental allergic encephalomyelitis (EAE) is mediated by neuroantigen-specific pro-inflammatory T cells of the Th1 and Th17 effector class. Th-17 cells can be clearly defined by expression of IL-17, but not IFN-γ, IL-2 or IL-3. Th1 cells do not express IL-17, but it is
[...] Read more.
Experimental allergic encephalomyelitis (EAE) is mediated by neuroantigen-specific pro-inflammatory T cells of the Th1 and Th17 effector class. Th-17 cells can be clearly defined by expression of IL-17, but not IFN-γ, IL-2 or IL-3. Th1 cells do not express IL-17, but it is unclear presently to what extent they co-express the cytokines canonically assigned to Th1 immunity (i.e., IFN-γ, IL-2 and IL-3) and whether CD4 cells producing these cytokines indeed belong to a single Th1 lineage. It is also unclear to what extent the Th1 response in EAE entails polyfunctional T cells that co-express IFN-γ and IL-2. Therefore, we dissected the Th1 cytokine signature of neuroantigen-specific CD4 cells studying at single cell resolution co-expression of IFN-γ, IL-2 and IL-3 using dual color cytokine ELISPOT analysis. Shortly after immunization, in the draining lymph nodes (dLN), the overall cytokine signature of the neuroantigen-specific CD4 cells was highly type 1-polarized, but IFN-γ, IL-2, and IL-3 were each secreted by different CD4 cells in a mutually exclusive manner. This single cell – single cytokine profile was stable through the course of chronic EAE–polyfunctional CD4 cells co-expressing IL-2 and IFN-γ presented less than 5% of the neuroantigen-specific T cells, even in the inflamed CNS itself. The neuroantigen-specific CD4 cells that expressed IFN-γ, IL-2 and IL-3 in a mutually exclusive manner exhibited similar functional avidities and kinetics of cytokine production, but showed different tissue distributions. These data suggest that Th1 cells do not belong to a single lineage, but different Th1 subpopulations jointly mediate Th1 immunity. Full article
(This article belongs to the Special Issue ELISPOT Research)
Figures

Review

Jump to: Research

Open AccessReview Modulation of Autophagy-Like Processes by Tumor Viruses
Cells 2012, 1(3), 204-247; doi:10.3390/cells1030204
Received: 16 May 2012 / Revised: 13 June 2012 / Accepted: 14 June 2012 / Published: 25 June 2012
Cited by 8 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses
[...] Read more.
Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview The Selectivity and Specificity of Autophagy in Drosophila
Cells 2012, 1(3), 248-262; doi:10.3390/cells1030248
Received: 23 May 2012 / Revised: 19 June 2012 / Accepted: 20 June 2012 / Published: 29 June 2012
PDF Full-text (93 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is a process of cellular self-degradation and is a major pathway for elimination of cytoplasmic material by the lysosomes. Autophagy is responsible for the degradation of damaged organelles and protein aggregates and therefore plays a significant role in cellular homeostasis. Despite the
[...] Read more.
Autophagy is a process of cellular self-degradation and is a major pathway for elimination of cytoplasmic material by the lysosomes. Autophagy is responsible for the degradation of damaged organelles and protein aggregates and therefore plays a significant role in cellular homeostasis. Despite the initial belief that autophagy is a nonselective bulk process, there is growing evidence during the last years that sequestration and degradation of cellular material by autophagy can be accomplished in a selective and specific manner. Given the role of autophagy and selective autophagy in several disease related processes such as tumorigenesis, neurodegeneration and infections, it is very important to dissect the molecular mechanisms of selective autophagy, in the context of the system and the organism. An excellent genetically tractable model organism to study autophagy is Drosophila, which appears to have a highly conserved autophagic machinery compared with mammals. However, the mechanisms of selective autophagy in Drosophila have been largely unexplored. The aim of this review is to summarize recent discoveries about the selectivity of autophagy in Drosophila. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview An Overview of Autophagy and Yeast Pseudohyphal Growth: Integration of Signaling Pathways during Nitrogen Stress
Cells 2012, 1(3), 263-283; doi:10.3390/cells1030263
Received: 9 May 2012 / Revised: 14 June 2012 / Accepted: 19 June 2012 / Published: 4 July 2012
Cited by 5 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
The budding yeast Saccharomyces cerevisiae responds to nutritional stress through the regulated activities of signaling pathways mediating autophagy and other conserved cellular processes. Autophagy has been studied intensely in yeast, where over 30 autophagy-related genes have been identified with defined roles enabling the
[...] Read more.
The budding yeast Saccharomyces cerevisiae responds to nutritional stress through the regulated activities of signaling pathways mediating autophagy and other conserved cellular processes. Autophagy has been studied intensely in yeast, where over 30 autophagy-related genes have been identified with defined roles enabling the formation of autophagic vesicles and their subsequent trafficking to the central yeast vacuole. Much less, however, is known regarding the regulatory mechanisms through which autophagy is integrated with other yeast stress responses. Nitrogen limitation initiates autophagy and pseudohyphal growth in yeast, the latter being a fascinating stress response characterized by the formation of multicellular chains or filaments of elongated cells. An increasing body of evidence suggests an interrelationship between processes responsive to nitrogen stress with cAMP-dependent PKA and the TOR kinase complex acting as key regulators of autophagy, pseudohyphal growth, and endocytosis. In this review, we will summarize our current understanding of the regulatory events controlling these processes. In particular, we explore the interplay between autophagy, polarized pseudohyphal growth, and to a lesser extent endocytosis, and posit that the integrated response of these processes in yeast is a critical point for further laboratory experimentation as a model of cellular responses to nitrogen limitation throughout the Eukaryota. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Regulation of the Autophagic Bcl-2/Beclin 1 Interaction
Cells 2012, 1(3), 284-312; doi:10.3390/cells1030284
Received: 14 May 2012 / Revised: 6 June 2012 / Accepted: 15 June 2012 / Published: 6 July 2012
Cited by 19 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an intracellular degradation process responsible for the delivery of cellular material to the lysosomes. One of the key mechanisms for control of autophagy is the modulation of the interaction between the autophagic protein Beclin 1 and the members of the anti-apoptotic
[...] Read more.
Autophagy is an intracellular degradation process responsible for the delivery of cellular material to the lysosomes. One of the key mechanisms for control of autophagy is the modulation of the interaction between the autophagic protein Beclin 1 and the members of the anti-apoptotic Bcl-2 family (e.g., Bcl-2, Bcl-XL and Mcl-1). This binding is regulated by a variety of proteins and compounds that are able to enhance or inhibit the Bcl-2/Beclin 1 interaction in order to repress or activate autophagy, respectively. In this review we will focus on this interaction and discuss its characteristics, relevance and regulation. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies
Cells 2012, 1(3), 325-345; doi:10.3390/cells1030325
Received: 4 May 2012 / Revised: 18 June 2012 / Accepted: 13 July 2012 / Published: 26 July 2012
Cited by 14 | PDF Full-text (352 KB) | HTML Full-text | XML Full-text
Abstract
Skeletal muscles are the agent of motion and one of the most important tissues responsible for the control of metabolism. The maintenance of muscle homeostasis is finely regulated by the balance between catabolic and anabolic process. Macroautophagy (or autophagy) is a catabolic process
[...] Read more.
Skeletal muscles are the agent of motion and one of the most important tissues responsible for the control of metabolism. The maintenance of muscle homeostasis is finely regulated by the balance between catabolic and anabolic process. Macroautophagy (or autophagy) is a catabolic process that provides the degradation of protein aggregation and damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagy flux is fundamental for the homeostasis of skeletal muscles during physiological situations and in response to stress. Defective as well as excessive autophagy is harmful for muscle health and has a pathogenic role in several forms of muscle diseases. This review will focus on the role of autophagy in muscle homeostasis and diseases. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Autophagy in Trypanosomatids
Cells 2012, 1(3), 346-371; doi:10.3390/cells1030346
Received: 28 June 2012 / Revised: 14 July 2012 / Accepted: 16 July 2012 / Published: 27 July 2012
Cited by 1 | PDF Full-text (1706 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is a ubiquitous eukaryotic process that also occurs in trypanosomatid parasites, protist organisms belonging to the supergroup Excavata, distinct from the supergroup Opistokontha that includes mammals and fungi. Half of the known yeast and mammalian AuTophaGy (ATG) proteins were detected in trypanosomatids,
[...] Read more.
Autophagy is a ubiquitous eukaryotic process that also occurs in trypanosomatid parasites, protist organisms belonging to the supergroup Excavata, distinct from the supergroup Opistokontha that includes mammals and fungi. Half of the known yeast and mammalian AuTophaGy (ATG) proteins were detected in trypanosomatids, although with low sequence conservation. Trypanosomatids such as Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for serious tropical diseases in humans. The parasites are transmitted by insects and, consequently, have a complicated life cycle during which they undergo dramatic morphological and metabolic transformations to adapt to the different environments. Autophagy plays a major role during these transformations. Since inhibition of autophagy affects the transformation, survival and/or virulence of the parasites, the ATGs offer promise for development of drugs against tropical diseases. Furthermore, various trypanocidal drugs have been shown to trigger autophagy-like processes in the parasites. It is inferred that autophagy is used by the parasites in an—not always successful—attempt to cope with the stress caused by the toxic compounds. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Regulation of Autophagy by Glucose in Mammalian Cells
Cells 2012, 1(3), 372-395; doi:10.3390/cells1030372
Received: 7 May 2012 / Revised: 22 June 2012 / Accepted: 13 July 2012 / Published: 27 July 2012
Cited by 12 | PDF Full-text (409 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also
[...] Read more.
Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focus on the signalling pathways by which environmental glucose directly, i.e., independently of insulin and glucagon, regulates autophagy in mammalian cells, but we will also briefly mention some data in yeast. Although glucose deprivation mainly induces autophagy via AMPK activation and the subsequent inhibition of mTORC1, we will also comment other signalling pathways, as well as evidences indicating that, under certain conditions, autophagy can be activated by glucose. A better understanding on how glucose regulates autophagy not only will expand our basic knowledge of this important cell process, but it will be also relevant to understand common human disorders, such as cancer and diabetes, in which glucose levels play an important role. Full article
(This article belongs to the Special Issue Autophagy)
Figures

Open AccessReview LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy
Cells 2012, 1(3), 396-408; doi:10.3390/cells1030396
Received: 13 June 2012 / Revised: 21 July 2012 / Accepted: 23 July 2012 / Published: 30 July 2012
Cited by 21 | PDF Full-text (600 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an intracellular degradative process with a number of roles, one of which can be the protection of eukaryotic cells from invading microbes. Microtubule-associated protein light-chain 3 (LC3) is a key autophagy-related protein that is recruited to the double-membrane autophagosome responsible for
[...] Read more.
Autophagy is an intracellular degradative process with a number of roles, one of which can be the protection of eukaryotic cells from invading microbes. Microtubule-associated protein light-chain 3 (LC3) is a key autophagy-related protein that is recruited to the double-membrane autophagosome responsible for sequestering material intended for delivery to lysosomes. GFP-LC3 is widely used as a marker of autophagosome formation as denoted by the formation of green puncta when viewed by fluorescence microscopy. Recently, it has been demonstrated that LC3 can be recruited to other membranes including single-membrane phagosomes, in a process termed LC3-associated phagocytosis (LAP). Thus, the observation of green puncta in cells can no longer, by itself, be taken as evidence of autophagy. This review will clarify those features of LAP which serve to distinguish it from autophagy and that make connections with host autophagic responses in terms of infection by microbial pathogens. More specifically, it will refer to concurrent studies of the mechanism by which LAP is triggered in comparison to autophagy. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Autophagy During Vertebrate Development
Cells 2012, 1(3), 428-448; doi:10.3390/cells1030428
Received: 9 May 2012 / Revised: 28 June 2012 / Accepted: 18 July 2012 / Published: 2 August 2012
Cited by 8 | PDF Full-text (1037 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an evolutionarily conserved catabolic process by which cells degrade their own components through the lysosomal machinery. In physiological conditions, the mechanism is tightly regulated and contributes to maintain a balance between synthesis and degradation in cells undergoing intense metabolic activities. Autophagy
[...] Read more.
Autophagy is an evolutionarily conserved catabolic process by which cells degrade their own components through the lysosomal machinery. In physiological conditions, the mechanism is tightly regulated and contributes to maintain a balance between synthesis and degradation in cells undergoing intense metabolic activities. Autophagy is associated with major tissue remodeling processes occurring through the embryonic, fetal and early postnatal periods of vertebrates. Here we survey current information implicating autophagy in cellular death, proliferation or differentiation in developing vertebrates. In developing systems, activation of the autophagic machinery could promote different outcomes depending on the cellular context. Autophagy is thus an extraordinary tool for the developing organs and tissues. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Role of Macroautophagy in Nutrient Homeostasis During Fungal Development and Pathogenesis
Cells 2012, 1(3), 449-463; doi:10.3390/cells1030449
Received: 2 May 2012 / Revised: 7 June 2012 / Accepted: 17 July 2012 / Published: 2 August 2012
Cited by 6 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
Macroautophagy is a non-selective, bulk degradation process conserved in eukaryotes. Response to starvation stress and/or regulation of nutrient breakdown/utilization is the major intracellular function of macroautophagy. Recent studies have revealed requirement for autophagy in diverse functions such as nutrient homeostasis, organelle degradation and
[...] Read more.
Macroautophagy is a non-selective, bulk degradation process conserved in eukaryotes. Response to starvation stress and/or regulation of nutrient breakdown/utilization is the major intracellular function of macroautophagy. Recent studies have revealed requirement for autophagy in diverse functions such as nutrient homeostasis, organelle degradation and programmed cell death in filamentous fungal pathogens, for proper morphogenesis and differentiation during critical steps of infection. In this review, we aim to summarize the physiological functions of autophagy in fungal virulence, with an emphasis on nutrient homeostasis in opportunistic human fungal pathogens and in the rice-blast fungus, Magnaporthe oryzae. We briefly summarize the role of autophagy on the host side: for resistance to, or subversion by, the pathogens. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy
Cells 2012, 1(3), 464-491; doi:10.3390/cells1030464
Received: 15 June 2012 / Revised: 9 July 2012 / Accepted: 19 July 2012 / Published: 3 August 2012
Cited by 9 | PDF Full-text (582 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy
[...] Read more.
Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy provides another programmed cell death pathway, known as Autophagic Cell Death (ACD). The induction of autophagy is a common outcome in PhotoDynamic Therapy (PDT), a two-step process involving the irradiation of photosensitizer (PS)-loaded cancer cells. Upon tissue oxygen interaction, PS provokes immediate and direct Reactive Oxygen Species (ROS)-induced damage to Endoplasmic Reticulum (ER), mitochondria, plasma membrane, and/or lysosomes. The main biological effects carried out in cancer PDT are direct cytotoxicity to tumor cells, vasculature damage and induction of inflammatory reactions stimulating immunological responses. The question about the role of autophagy in PDT and its putative immunological impact is hotly controversial and largely studied in recent times. This review deals with the induction of autophagy in PDT protocols and its dual role, also considering its interrelationship with apoptosis, the preferential cell death program triggered in the photodynamic process. Full article
(This article belongs to the Special Issue Autophagy)
Figures

Open AccessReview The Role of Autophagy in Crohn’s Disease
Cells 2012, 1(3), 492-519; doi:10.3390/cells1030492
Received: 18 June 2012 / Revised: 20 July 2012 / Accepted: 23 July 2012 / Published: 3 August 2012
Cited by 2 | PDF Full-text (669 KB) | HTML Full-text | XML Full-text
Abstract
(Macro)-autophagy is a homeostatic process by which eukaryotic cells dispose of protein aggregates and damaged organelles. Autophagy is also used to degrade micro-organisms that invade intracellularly in a process termed xenophagy. Genome-wide association scans have recently identified autophagy genes as conferring susceptibility to
[...] Read more.
(Macro)-autophagy is a homeostatic process by which eukaryotic cells dispose of protein aggregates and damaged organelles. Autophagy is also used to degrade micro-organisms that invade intracellularly in a process termed xenophagy. Genome-wide association scans have recently identified autophagy genes as conferring susceptibility to Crohn’s disease (CD), one of the chronic inflammatory bowel diseases, with evidence suggesting that CD arises from a defective innate immune response to enteric bacteria. Here we review the emerging role of autophagy in CD, with particular focus on xenophagy and enteric E. coli strains with an adherent and invasive phenotype that have been consistently isolated from CD patients with ileal disease. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Autophagy and Cancer
Cells 2012, 1(3), 520-534; doi:10.3390/cells1030520
Received: 14 June 2012 / Revised: 28 June 2012 / Accepted: 30 July 2012 / Published: 13 August 2012
Cited by 12 | PDF Full-text (1173 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Autophagy is a housekeeping survival mechanism with a protective function against stress conditions. However, when stress severity or duration increases, it may promote cell death. Paradoxically, autophagy favors cancer development, since cancer cells could enhance their proliferation potential (thus becoming able to resist
[...] Read more.
Autophagy is a housekeeping survival mechanism with a protective function against stress conditions. However, when stress severity or duration increases, it may promote cell death. Paradoxically, autophagy favors cancer development, since cancer cells could enhance their proliferation potential (thus becoming able to resist anticancer therapy) thanks to the energetic supply provided by organelle degradation typically driven by autophagy following a stepwise pathway. The main actors of the autophagic machinery as well as the features shared with apoptosis will be described. Special attention will be paid to the effects of autophagy manipulation. Full article
(This article belongs to the Special Issue Autophagy)
Figures

Open AccessReview Updates from the Intestinal Front Line: Autophagic Weapons against Inflammation and Cancer
Cells 2012, 1(3), 535-557; doi:10.3390/cells1030535
Received: 7 May 2012 / Revised: 4 July 2012 / Accepted: 1 August 2012 / Published: 21 August 2012
PDF Full-text (435 KB) | HTML Full-text | XML Full-text
Abstract
The intestine lies at the interface between the organism and its environment and responds to infection/inflammation in a multi-leveled manner, potentially leading to chronic inflammatory pathologies and cancer formation. Indeed, the immune response at the intestinal epithelium has been found to be involved
[...] Read more.
The intestine lies at the interface between the organism and its environment and responds to infection/inflammation in a multi-leveled manner, potentially leading to chronic inflammatory pathologies and cancer formation. Indeed, the immune response at the intestinal epithelium has been found to be involved in the origin and development of colorectal cancer, which is the third most commonly diagnosed neoplastic disease. Among the mechanisms induced upon inflammation, autophagy appears as a defensive strategy for the clearance of invading microbes and intracellular waste components. Autophagy has also been found to play an important role in colorectal cancer, where it seems to have a pro-survival or pro-death function depending on the stage of the neoplastic process. In this paper we discuss the dual role of autophagy in colorectal cancer and review evidence showing that modulation of autophagy affects the immune response and cancer biology. The study of key players involved in autophagy might contribute to the design of new approaches for colorectal cancer, consisting in combined therapies capable of modifying cancer-specific metabolism rather than simply evoking a generic apoptotic and/or autophagic response, thus enhancing the efficacy of currently used drugs and treatments. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Autophagy and Transporter-Based Multi-Drug Resistance
Cells 2012, 1(3), 558-575; doi:10.3390/cells1030558
Received: 17 June 2012 / Revised: 11 August 2012 / Accepted: 16 August 2012 / Published: 23 August 2012
Cited by 8 | PDF Full-text (697 KB) | HTML Full-text | XML Full-text
Abstract
All the therapeutic strategies for treating cancers aim at killing the cancer cells via apoptosis (programmed cell death type I). Defective apoptosis endow tumor cells with survival. The cell can respond to such defects with autophagy. Autophagy is a cellular process by which
[...] Read more.
All the therapeutic strategies for treating cancers aim at killing the cancer cells via apoptosis (programmed cell death type I). Defective apoptosis endow tumor cells with survival. The cell can respond to such defects with autophagy. Autophagy is a cellular process by which cytoplasmic material is either degraded to maintain homeostasis or recycled for energy and nutrients in starvation. A plethora of evidence has shown that the role of autophagy in tumors is complex. A lot of effort is needed to underline the functional status of autophagy in tumor progression and treatment, and elucidate how to tweak autophagy to treat cancer. Furthermore, during the treatment of cancer, the limitation for the cure rate and survival is the phenomenon of multi drug resistance (MDR). The development of MDR is an intricate process that could be regulated by drug transporters, enzymes, anti-apoptotic genes or DNA repair mechanisms. Reports have shown that autophagy has a dual role in MDR. Furthermore, it has been reported that activation of a death pathway may overcome MDR, thus pointing the importance of other death pathways to regulate tumor cell progression and growth. Therefore, in this review we will discuss the role of autophagy in MDR tumors and a possible link amongst these phenomena. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Heavy Metals and Metalloids as Autophagy Inducing Agents: Focus on Cadmium and Arsenic
Cells 2012, 1(3), 597-616; doi:10.3390/cells1030597
Received: 19 July 2012 / Revised: 10 August 2012 / Accepted: 14 August 2012 / Published: 27 August 2012
Cited by 19 | PDF Full-text (456 KB) | HTML Full-text | XML Full-text
Abstract
In recent years, research on the autophagic process has greatly increased, invading the fields of biology and medicine. Several markers of the autophagic process have been discovered and various strategies have been reported studying this molecular process in different biological systems in both
[...] Read more.
In recent years, research on the autophagic process has greatly increased, invading the fields of biology and medicine. Several markers of the autophagic process have been discovered and various strategies have been reported studying this molecular process in different biological systems in both physiological and stress conditions. Furthermore, mechanisms of metalloid- or heavy metal-induced toxicity continue to be of interest given the ubiquitous nature and distribution of these contaminants in the environment where they often play the role of pollutants of numerous organisms. The aim of this review is a critical analysis and correlation of knowledge of autophagic mechanisms studied under stress for the most common arsenic (As) and cadmium (Cd) compounds. In this review we report data obtained in different experimental models for each compound, highlighting similarities and/or differences in the activation of autophagic processes. A more detailed discussion will concern the activation of autophagy in Cd-exposed sea urchin embryo since it is a suitable model system that is very sensitive to environmental stress, and Cd is one of the most studied heavy metal inductors of stress and modulator of different factors such as: protein kinase and phosphatase, caspases, mitochondria, heat shock proteins, metallothioneins, transcription factors, reactive oxygen species, apoptosis and autophagy. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview How Human Tumor Viruses Make Use of Autophagy
Cells 2012, 1(3), 617-630; doi:10.3390/cells1030617
Received: 1 July 2012 / Revised: 11 August 2012 / Accepted: 21 August 2012 / Published: 27 August 2012
Cited by 2 | PDF Full-text (299 KB) | HTML Full-text | XML Full-text
Abstract
Viruses commandeer regulatory pathways of their hosts to optimize their success as cellular parasites. The human tumor viruses, Epstein-Barr Virus (EBV), Kaposi’s Sarcoma Herpesvirus (KSHV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) all affect autophagy for their own ends. EBV and
[...] Read more.
Viruses commandeer regulatory pathways of their hosts to optimize their success as cellular parasites. The human tumor viruses, Epstein-Barr Virus (EBV), Kaposi’s Sarcoma Herpesvirus (KSHV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) all affect autophagy for their own ends. EBV and KSHV regulate it during latent infections, a phase when no progeny virus is produced, while HBV and HCV use autophagy to promote their productive infections. Here we shall compare and contrast how these human tumor viruses regulate autophagy and what they gain by the appropriation of this cellular pathway. Full article
(This article belongs to the Special Issue Autophagy)
Open AccessReview Stress Response Pathways in Ameloblasts: Implications for Amelogenesis and Dental Fluorosis
Cells 2012, 1(3), 631-645; doi:10.3390/cells1030631
Received: 24 July 2012 / Revised: 2 August 2012 / Accepted: 20 August 2012 / Published: 30 August 2012
Cited by 7 | PDF Full-text (223 KB) | HTML Full-text | XML Full-text
Abstract
Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental
[...] Read more.
Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental fluorosis after childhood exposure to excess fluoride, an elemental agent used to increase enamel hardness and prevent dental caries. Currently the molecular mechanism responsible for dental fluorosis remains unknown; however, recent work suggests dental fluorosis may be the result of activated stress response pathways in ameloblasts during the development of permanent teeth. Using fluorosis as an example, the role of stress response pathways during enamel maturation is discussed. Full article
(This article belongs to the Special Issue Cellular Stress Response)
Open AccessReview Virus-Heat Shock Protein Interaction and a Novel Axis for Innate Antiviral Immunity
Cells 2012, 1(3), 646-666; doi:10.3390/cells1030646
Received: 1 August 2012 / Revised: 24 August 2012 / Accepted: 27 August 2012 / Published: 11 September 2012
Cited by 8 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text
Abstract
Virus infections induce heat shock proteins that in turn enhance virus gene expression, a phenomenon that is particularly well characterized for the major inducible 70 kDa heat shock protein (hsp70). However, hsp70 is also readily induced by fever, a phylogenetically conserved response to
[...] Read more.
Virus infections induce heat shock proteins that in turn enhance virus gene expression, a phenomenon that is particularly well characterized for the major inducible 70 kDa heat shock protein (hsp70). However, hsp70 is also readily induced by fever, a phylogenetically conserved response to microbial infections, and when released from cells, hsp70 can stimulate innate immune responses through toll like receptors 2 and 4 (TLR2 and 4). This review examines how the virus-hsp70 relationship can lead to host protective innate antiviral immunity, and the importance of hsp70 dependent stimulation of virus gene expression in this host response. Beginning with the well-characterized measles virus-hsp70 relationship and the mouse model of neuronal infection in brain, we examine data indicating that the innate immune response is not driven by intracellular sensors of pathogen associated molecular patterns, but rather by extracellular ligands signaling through TLR2 and 4. Specifically, we address the relationship between virus gene expression, extracellular release of hsp70 (as a damage associated molecular pattern), and hsp70-mediated induction of antigen presentation and type 1 interferons in uninfected macrophages as a novel axis of antiviral immunity. New data are discussed that examines the more broad relevance of this protective mechanism using vesicular stomatitis virus, and a review of the literature is presented that supports the probable relevance to both RNA and DNA viruses and for infections both within and outside of the central nervous system. Full article
(This article belongs to the Special Issue Cellular Stress Response)

Journal Contact

MDPI AG
Cells Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
cells@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Cells
Back to Top