ijms-logo

Journal Browser

Journal Browser

Programmed Cell Death and Oxidative Stress

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (25 September 2023) | Viewed by 21249

Special Issue Editor

Special Issue Information

Dear Colleagues, 

Cells that constitute aerobic organisms are continuously exposed to reactive oxygen species (ROS), whose accumulation often initiates oxidative stress. Importantly, oxidative stress plays a critical role in the determination of cell fate by inducing cellular responses, such as proliferation, differentiation, and programmed cell death. Accumulating evidence indicates that oxidative stress initiates various forms of programmed cell death including apoptosis, necroptosis, pyroptosis, parthanatos, and ferroptosis. Moreover, all types of oxidative-stress-induced cell death are closely associated with a wide variety of diseases. For this Special Issue, studies of a wide range of signaling mechanisms and pathological processes related to oxidative stress-induced cell death are welcome.

Dr. Takuya Noguchi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oxidative stress
  • programmed cell death
  • cellular stresses
  • senescence
  • cytotoxicity
  • cancer
  • neurodegenerative disease
  • inflammatory disease
  • organelle stress

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issues

Published Papers (9 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 5580 KiB  
Article
Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
by Runbo Li, Hirohito Kato, Chihiro Fumimoto, Yurika Nakamura, Kimihiro Yoshimura, Emika Minagawa, Keiju Omatsu, Chizuko Ogata, Yoichiro Taguchi and Makoto Umeda
Int. J. Mol. Sci. 2023, 24(20), 15314; https://doi.org/10.3390/ijms242015314 - 18 Oct 2023
Viewed by 1533
Abstract
Intracellular nutrient metabolism, particularly the metabolism of essential amino acids (EAAs), is crucial for cellular functions, including energy production and redox homeostasis. An EAA deficiency can lead to cellular dysfunction and oxidative stress. This study explores the mechanisms underlying cellular responses to EAA [...] Read more.
Intracellular nutrient metabolism, particularly the metabolism of essential amino acids (EAAs), is crucial for cellular functions, including energy production and redox homeostasis. An EAA deficiency can lead to cellular dysfunction and oxidative stress. This study explores the mechanisms underlying cellular responses to EAA starvation, focusing on ROS-induced DNA damage and apoptosis. MC3T3-E1 cells were subjected to EAA starvation, and various assays were conducted to assess cell proliferation, survival, DNA damage, and apoptosis. The antioxidant N-acetylcysteine (NAC) was employed to block ROS formation and mitigate cellular damage. Gene expression and Western blot analyses were performed to elucidate molecular pathways. EAA starvation-induced ROS generation, DNA damage, and apoptosis in MC3T3-E1 cells. NAC administration effectively reduced DNA damage and apoptosis, highlighting the pivotal role of ROS in mediating these cellular responses during EAA deficiency. This study demonstrates that EAA starvation triggers ROS-mediated DNA damage and apoptosis, offering insights into the intricate interplay between nutrient deficiency, oxidative stress, and programmed cell death. NAC emerges as a potential therapeutic intervention to counteract these adverse effects. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

17 pages, 8932 KiB  
Article
Exploring the Role of Different Cell-Death-Related Genes in Sepsis Diagnosis Using a Machine Learning Algorithm
by Xuesong Wang, Ziyi Wang, Zhe Guo, Ziwen Wang, Feng Chen and Zhong Wang
Int. J. Mol. Sci. 2023, 24(19), 14720; https://doi.org/10.3390/ijms241914720 - 29 Sep 2023
Cited by 2 | Viewed by 1362
Abstract
Sepsis, a disease caused by severe infection, has a high mortality rate. At present, there is a lack of reliable algorithmic models for biomarker mining and diagnostic model construction for sepsis. Programmed cell death (PCD) has been shown to play a vital role [...] Read more.
Sepsis, a disease caused by severe infection, has a high mortality rate. At present, there is a lack of reliable algorithmic models for biomarker mining and diagnostic model construction for sepsis. Programmed cell death (PCD) has been shown to play a vital role in disease occurrence and progression, and different PCD-related genes have the potential to be targeted for the treatment of sepsis. In this paper, we analyzed PCD-related genes in sepsis. Implicated PCD processes include apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, and alkaliptosis. We screened for diagnostic-related genes and constructed models for diagnosing sepsis using multiple machine-learning models. In addition, the immune landscape of sepsis was analyzed based on the diagnosis-related genes that were obtained. In this paper, 10 diagnosis-related genes were screened for using machine learning algorithms, and diagnostic models were constructed. The diagnostic model was validated in the internal and external test sets, and the Area Under Curve (AUC) reached 0.7951 in the internal test set and 0.9627 in the external test set. Furthermore, we verified the diagnostic gene via a qPCR experiment. The diagnostic-related genes and diagnostic genes obtained in this paper can be utilized as a reference for clinical sepsis diagnosis. The results of this study can act as a reference for the clinical diagnosis of sepsis and for target discovery for potential therapeutic drugs. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

16 pages, 6400 KiB  
Article
Arginine Expedites Erastin-Induced Ferroptosis through Fumarate
by Xinxin Guo, Yubo Guo, Jiahuan Li, Qian Liu and Hao Wu
Int. J. Mol. Sci. 2023, 24(19), 14595; https://doi.org/10.3390/ijms241914595 - 27 Sep 2023
Cited by 7 | Viewed by 1502
Abstract
Ferroptosis is a newly characterized form of programmed cell death. The fundamental biochemical feature of ferroptosis is the lethal accumulation of iron-catalyzed lipid peroxidation. It has gradually been recognized that ferroptosis is implicated in the pathogenesis of a variety of human diseases. Increasing [...] Read more.
Ferroptosis is a newly characterized form of programmed cell death. The fundamental biochemical feature of ferroptosis is the lethal accumulation of iron-catalyzed lipid peroxidation. It has gradually been recognized that ferroptosis is implicated in the pathogenesis of a variety of human diseases. Increasing evidence has shed light on ferroptosis regulation by amino acid metabolism. Herein, we report that arginine deprivation potently inhibits erastin-induced ferroptosis, but not RSL3-induced ferroptosis, in several types of mammalian cells. Arginine presence reduces the intracellular glutathione (GSH) level by sustaining the biosynthesis of fumarate, which functions as a reactive α,β-unsaturated electrophilic metabolite and covalently binds to GSH to generate succinicGSH. siRNA-mediated knockdown of argininosuccinate lyase, the critical urea cycle enzyme directly catalyzing the biosynthesis of fumarate, significantly decreases cellular fumarate and thus relieves erastin-induced ferroptosis in the presence of arginine. Furthermore, fumarate is decreased during erastin exposure, suggesting that a protective mechanism exists to decelerate GSH depletion in response to pro-ferroptotic insult. Collectively, this study reveals the ferroptosis regulation by the arginine metabolism and expands the biochemical functionalities of arginine. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

13 pages, 2305 KiB  
Article
Novel Insights in the Potential of Halogenated Polyketide–Peptide Molecules as Lead Compounds in Cancer Drug Discovery
by Valentina Pellicioni, Germana Esposito, Giulia Greco, Ivan Cruz-Chamorro, Fabio Ferrini, Piero Sestili, Roberta Teta, Carmela Fimognari and Valeria Costantino
Int. J. Mol. Sci. 2023, 24(7), 6208; https://doi.org/10.3390/ijms24076208 - 25 Mar 2023
Viewed by 1641
Abstract
In this interdisciplinary study, we selected two compounds, namely, smenamide A, a peptide–polyketide, and smenolactone D, a polyketide, as models because they are representative of two different classes of molecules isolated from the marine sponge Smenospongia aurea. The organic extract of Smenospongia aurea [...] Read more.
In this interdisciplinary study, we selected two compounds, namely, smenamide A, a peptide–polyketide, and smenolactone D, a polyketide, as models because they are representative of two different classes of molecules isolated from the marine sponge Smenospongia aurea. The organic extract of Smenospongia aurea was analyzed using a combination of high-resolution LC-MS/MS and molecular networking, a recently developed method for automated LC-MS data analysis. The analyses were targeted to highlight clusters made by chlorinated compounds present in the extracts. Then, the two model compounds were analyzed for their bioactivity. Data reported here show that smenamide A did not exhibit a cytotoxic effect, while smenolactone D was cytotoxic on different tumor cell lines and was able to induce different types of cell death, including ferroptosis and apoptosis. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

11 pages, 3338 KiB  
Article
Mechanical Regulation of Redox Balance via the Induction of the PIN1/NRF2/ARE Axis in Pancreatic Cancer
by Chen Liang, Zeyin Rong, Abudureyimu Tuerhong, Qingcai Meng, Jie Hua, Jiang Liu, Bo Zhang, Wei Wang, Xianjun Yu, Si Shi and Jin Xu
Int. J. Mol. Sci. 2023, 24(4), 3476; https://doi.org/10.3390/ijms24043476 - 9 Feb 2023
Cited by 2 | Viewed by 1841
Abstract
Pancreatic cancer is one of the most lethal malignancies. Desmoplastic stroma and metabolic reprogramming are two hallmarks of pancreatic cancer that support its malignant biological behaviors. However, the underlying mechanism by which the stroma maintain the redox balance remains unclear in pancreatic ductal [...] Read more.
Pancreatic cancer is one of the most lethal malignancies. Desmoplastic stroma and metabolic reprogramming are two hallmarks of pancreatic cancer that support its malignant biological behaviors. However, the underlying mechanism by which the stroma maintain the redox balance remains unclear in pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrated that the physical properties of the stroma could regulate the expression of PIN1 in pancreatic cancer cells. Moreover, we found that hard matrix-cultured pancreatic cancer cells induced the upregulation of PIN1 expression. Since PIN1 maintained redox balance via synergistic activation of NRF2 transcription, PIN1 promoted the expression of NRF2 to induce the expression of intracellular antioxidant response element (ARE)-driven genes. Consequently, the antioxidant stress ability of PDAC was increased, and the intracellular level of reactive oxygen species (ROS) was decreased. Thus, PIN1 is expected to be an important target for the treatment of PDAC, especially PDAC with an exuberant desmoplastic stroma. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

Review

Jump to: Research

21 pages, 2436 KiB  
Review
NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus
by Dong-Oh Moon
Int. J. Mol. Sci. 2024, 25(1), 342; https://doi.org/10.3390/ijms25010342 - 26 Dec 2023
Cited by 4 | Viewed by 1794
Abstract
This review offers an in-depth exploration of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) in metabolic health. It delves into how NADPH affects insulin secretion, influences insulin resistance, and plays a role in ferroptosis. NADPH, a critical cofactor in cellular antioxidant systems and lipid synthesis, [...] Read more.
This review offers an in-depth exploration of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) in metabolic health. It delves into how NADPH affects insulin secretion, influences insulin resistance, and plays a role in ferroptosis. NADPH, a critical cofactor in cellular antioxidant systems and lipid synthesis, plays a central role in maintaining metabolic homeostasis. In adipocytes and skeletal muscle, NADPH influences the pathophysiology of insulin resistance, a hallmark of metabolic disorders such as type 2 diabetes and obesity. The review explores the mechanisms by which NADPH contributes to or mitigates insulin resistance, including its role in lipid and reactive oxygen species (ROS) metabolism. Parallelly, the paper investigates the dual nature of NADPH in the context of pancreatic β-cell health, particularly in its relation to ferroptosis, an iron-dependent form of programmed cell death. While NADPH’s antioxidative properties are crucial for preventing oxidative damage in β-cells, its involvement in lipid metabolism can potentiate ferroptotic pathways under certain pathological conditions. This complex relationship underscores the delicate balance of NADPH homeostasis in pancreatic health and diabetes pathogenesis. By integrating findings from recent studies, this review aims to illuminate the nuanced roles of NADPH in different tissues and its potential as a therapeutic target. Understanding these dynamics offers vital insights into the development of more effective strategies for managing insulin resistance and preserving pancreatic β-cell function, thereby advancing the treatment of metabolic diseases. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

42 pages, 6747 KiB  
Review
The Role of Hydrogen Sulfide in Regulation of Cell Death following Neurotrauma and Related Neurodegenerative and Psychiatric Diseases
by Stanislav Rodkin, Chizaram Nwosu, Alexander Sannikov, Margarita Raevskaya, Alexander Tushev, Inna Vasilieva and Mitkhat Gasanov
Int. J. Mol. Sci. 2023, 24(13), 10742; https://doi.org/10.3390/ijms241310742 - 28 Jun 2023
Cited by 9 | Viewed by 3540
Abstract
Injuries of the central (CNS) and peripheral nervous system (PNS) are a serious problem of the modern healthcare system. The situation is complicated by the lack of clinically effective neuroprotective drugs that can protect damaged neurons and glial cells from death. In addition, [...] Read more.
Injuries of the central (CNS) and peripheral nervous system (PNS) are a serious problem of the modern healthcare system. The situation is complicated by the lack of clinically effective neuroprotective drugs that can protect damaged neurons and glial cells from death. In addition, people who have undergone neurotrauma often develop mental disorders and neurodegenerative diseases that worsen the quality of life up to severe disability and death. Hydrogen sulfide (H2S) is a gaseous signaling molecule that performs various cellular functions in normal and pathological conditions. However, the role of H2S in neurotrauma and mental disorders remains unexplored and sometimes controversial. In this large-scale review study, we examined the various biological effects of H2S associated with survival and cell death in trauma to the brain, spinal cord, and PNS, and the signaling mechanisms underlying the pathogenesis of mental illnesses, such as cognitive impairment, encephalopathy, depression and anxiety disorders, epilepsy and chronic pain. We also studied the role of H2S in the pathogenesis of neurodegenerative diseases: Alzheimer’s disease (AD) and Parkinson’s disease (PD). In addition, we reviewed the current state of the art study of H2S donors as neuroprotectors and the possibility of their therapeutic uses in medicine. Our study showed that H2S has great neuroprotective potential. H2S reduces oxidative stress, lipid peroxidation, and neuroinflammation; inhibits processes associated with apoptosis, autophagy, ferroptosis and pyroptosis; prevents the destruction of the blood-brain barrier; increases the expression of neurotrophic factors; and models the activity of Ca2+ channels in neurotrauma. In addition, H2S activates neuroprotective signaling pathways in psychiatric and neurodegenerative diseases. However, high levels of H2S can cause cytotoxic effects. Thus, the development of H2S-associated neuroprotectors seems to be especially relevant. However, so far, all H2S modulators are at the stage of preclinical trials. Nevertheless, many of them show a high neuroprotective effect in various animal models of neurotrauma and related disorders. Despite the fact that our review is very extensive and detailed, it is well structured right down to the conclusions, which will allow researchers to quickly find the proper information they are interested in. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Graphical abstract

39 pages, 7369 KiB  
Review
The Role of Gasotransmitter-Dependent Signaling Mechanisms in Apoptotic Cell Death in Cardiovascular, Rheumatic, Kidney, and Neurodegenerative Diseases and Mental Disorders
by Stanislav Rodkin, Chizaram Nwosu, Alexander Sannikov, Anton Tyurin, Vasilii Sergeevich Chulkov, Margarita Raevskaya, Alexey Ermakov, Evgeniya Kirichenko and Mitkhat Gasanov
Int. J. Mol. Sci. 2023, 24(7), 6014; https://doi.org/10.3390/ijms24076014 - 23 Mar 2023
Cited by 11 | Viewed by 2990
Abstract
Cardiovascular, rheumatic, kidney, and neurodegenerative diseases and mental disorders are a common cause of deterioration in the quality of life up to severe disability and death worldwide. Many pathological conditions, including this group of diseases, are based on increased cell death through apoptosis. [...] Read more.
Cardiovascular, rheumatic, kidney, and neurodegenerative diseases and mental disorders are a common cause of deterioration in the quality of life up to severe disability and death worldwide. Many pathological conditions, including this group of diseases, are based on increased cell death through apoptosis. It is known that this process is associated with signaling pathways controlled by a group of gaseous signaling molecules called gasotransmitters. They are unique messengers that can control the process of apoptosis at different stages of its implementation. However, their role in the regulation of apoptotic signaling in these pathological conditions is often controversial and not completely clear. This review analyzes the role of nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and sulfur dioxide (SO2) in apoptotic cell death in cardiovascular, rheumatic, kidney, and neurodegenerative diseases. The signaling processes involved in apoptosis in schizophrenia, bipolar, depressive, and anxiety disorders are also considered. The role of gasotransmitters in apoptosis in these diseases is largely determined by cell specificity and concentration. NO has the greatest dualism; scales are more prone to apoptosis. At the same time, CO, H2S, and SO2 are more involved in cytoprotective processes. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Graphical abstract

18 pages, 2203 KiB  
Review
Unscrambling the Role of Redox-Active Biometals in Dopaminergic Neuronal Death and Promising Metal Chelation-Based Therapy for Parkinson’s Disease
by Alfredo Gonzalez-Alcocer, Ana Patricia Duarte-Jurado, Adolfo Soto-Dominguez, Maria de Jesus Loera-Arias, Eliud Enrique Villarreal-Silva, Odila Saucedo-Cardenas, Roberto Montes de Oca-Luna, Aracely Garcia-Garcia and Humberto Rodriguez-Rocha
Int. J. Mol. Sci. 2023, 24(2), 1256; https://doi.org/10.3390/ijms24021256 - 9 Jan 2023
Cited by 6 | Viewed by 2878
Abstract
Biometals are all metal ions that are essential for all living organisms. About 40% of all enzymes with known structures require biometals to function correctly. The main target of damage by biometals is the central nervous system (CNS). Biometal dysregulation (metal deficiency or [...] Read more.
Biometals are all metal ions that are essential for all living organisms. About 40% of all enzymes with known structures require biometals to function correctly. The main target of damage by biometals is the central nervous system (CNS). Biometal dysregulation (metal deficiency or overload) is related to pathological processes. Chronic occupational and environmental exposure to biometals, including iron and copper, is related to an increased risk of developing Parkinson’s disease (PD). Indeed, biometals have been shown to induce a dopaminergic neuronal loss in the substantia nigra. Although the etiology of PD is still unknown, oxidative stress dysregulation, mitochondrial dysfunction, and inhibition of both the ubiquitin–proteasome system (UPS) and autophagy are related to dopaminergic neuronal death. Herein, we addressed the involvement of redox-active biometals, iron, and copper, as oxidative stress and neuronal death inducers, as well as the current metal chelation-based therapy in PD. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress)
Show Figures

Figure 1

Back to TopTop