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Molecular Mechanisms of Adaptation to Hypoxia 2.0

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 9697

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Special Issue Editors

Dr. Elena Rybnikova

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Guest Editor

Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg (ex Leningrad), Russia
Interests: hypoxia/ischemia; hypoxic tolerance of the brain; hypoxic signalling; neuroendocrine factors
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Ludmila D. Lukyanova

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Guest Editor

Institute of General Pathology and Pathophysiology, Baltijskaya Str. 8., 125315 Moscow, Russia
Interests: mitochondria; bioenergetics; hypoxia; adaptation; energy metabolism; succinate; HIF-1
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Impairment of the oxygen homeostasis of the body can result in the development of hypoxic/ischemic states, accompanied by multi-component multi-organ pathologies involving changes in a wide range of functional and metabolic systems. The regulation and correction of this complex process is possible through the increase of cellular and systemic resistance to oxygen insufficiency. Intensive study of the mechanisms contributing to the formation of hypoxic tolerance in cells and tissues is not only of great theoretical importance, but is also necessary to solve many problems of practical medicine. According to the modern concepts, the triggers and targets of hypoxic/ischemic states are molecular processes occurring at the cellular level. In the last two decades, significant advances have been made in their understanding; however, a number of important questions remain unresolved. For this Special Issue we would like to invite papers reporting new knowledge on the understudied questions. These include but are not limited to the following:

The mechanisms controlling and regulating the oxygen sensing of cells, their interactions, and their role in intracellular signaling in hypoxia;
The molecular mechanisms contributing to the formation of urgent and long-term cellular and systemic adaptation to hypoxia;
Variability of these processes depending on the characteristics of hypoxia (strength, duration, regime features);
Search for the optimal conditions for the induction of hypoxic tolerance;
Molecular approaches to elaborating the methods of anti-hypoxic protection which accelerate and facilitate the formation of urgent and long-term mechanisms of adaptation to oxygen deficiency.

Dr. Elena Rybnikova
Prof. Dr. Ludmila D. Lukyanova
Guest Editors

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

hypoxia\ischemia
hypoxic injury and tolerance
oxygen sensing
hypoxic signaling
hypoxia-inducible factors
HIF-1
mitochondria
succinate

Published Papers (5 papers)

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Research

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13 pages, 3355 KiB

Open AccessArticle

Dunaliella salina Alga Protects against Myocardial Ischemia/Reperfusion Injury by Attenuating TLR4 Signaling

by Chin-Feng Tsai, Hui-Wen Lin, Jiuan-Miaw Liao, Ke-Min Chen, Jen-Wei Tsai, Chia-Sung Chang, Chia-Yu Chou, Hsing-Hui Su, Pei-Hsun Liu, Ya-Chun Chu, Yi-Hsin Wang, Meilin Wang and Shiang-Suo Huang

Int. J. Mol. Sci. 2023, 24(4), 3871; https://doi.org/10.3390/ijms24043871 - 15 Feb 2023

Cited by 1 | Viewed by 1538

Abstract

Myocardial ischemia/reperfusion (I/R) injury is marked by rapid increase in inflammation and not only results in myocardial apoptosis but also compromises the myocardial function. Dunaliella salina (D. salina), a halophilic unicellular microalga, has been used as a provitamin A carotenoid supplement and color additive. Several studies have reported that D. salina extract could attenuate lipopolysaccharides-induced inflammatory effects and regulate the virus-induced inflammatory response in macrophages. However, the effects of D. salina on myocardial I/R injury remain unknown. Therefore, we aimed to investigate the cardioprotection of D. salina extract in rats subjected to myocardial I/R injury that was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion. Compared with the vehicle group, the myocardial infarct size significantly decreased in rats that were pre-treated with D. salina. D. salina significantly attenuated the expressions of TLR4, COX-2 and the activity of STAT1, JAK2, IκB, NF-κB. Furthermore, D. salina significantly inhibited the activation of caspase-3 and the levels of Beclin-1, p62, LC3-I/II. This study is the first to report that the cardioprotective effects of D. salina may mediate anti-inflammatory and anti-apoptotic activities and decrease autophagy through the TLR4-mediated signaling pathway to antagonize myocardial I/R injury. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptation to Hypoxia 2.0)

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14 pages, 2016 KiB

Open AccessArticle

Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model

by Inês Serrenho, Carla M. Cardoso, Mário Grãos, Alexandra Dinis, Bruno Manadas and Graça Baltazar

Int. J. Mol. Sci. 2023, 24(1), 257; https://doi.org/10.3390/ijms24010257 - 23 Dec 2022

Cited by 3 | Viewed by 1528

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term disability in the perinatal period. Currently, therapeutic hypothermia is the standard of care for this condition with modest efficacy and strict enrollment criteria. Therapy with umbilical cord blood cells (UCBC) has come forward as a strong candidate for the treatment of neonatal HIE, but no preclinical studies have yet compared the action of UCBC combined with hypothermia (HT) with the action of each therapy by itself. Thus, to evaluate the potential of each therapeutic approach, a hypoxic-ischemic brain lesion was induced in postnatal day ten rat pups; two hours later, HT was applied for 4 h; and 24, 48, and 72 h post-injury, UCBC were administered intravenously. The neonatal hypoxic-ischemic injury led to a brain lesion involving about 48% of the left hemisphere that was not improved by HT (36%) or UCBC alone (28%), but only with the combined therapies (25%; p = 0.0294). Moreover, a decrease in glial reactivity and improved functional outcomes were observed in both groups treated with UCBC. Overall, these results support UCBC as a successful therapeutic approach for HIE, even when treatment with therapeutic hypothermia is not possible. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptation to Hypoxia 2.0)

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31 pages, 4358 KiB

Open AccessArticle

The Role of Mitochondrial Enzymes, Succinate-Coupled Signaling Pathways and Mitochondrial Ultrastructure in the Formation of Urgent Adaptation to Acute Hypoxia in the Myocardium

by Elita Germanova, Natalya Khmil, Lyubov Pavlik, Irina Mikheeva, Galina Mironova and Ludmila Lukyanova

Int. J. Mol. Sci. 2022, 23(22), 14248; https://doi.org/10.3390/ijms232214248 - 17 Nov 2022

Cited by 8 | Viewed by 1693

Abstract

The effect of a single one-hour exposure to three modes of hypobaric hypoxia (HBH) differed in the content of O₂ in inhaled air (FiO₂—14%, 10%, 8%) in the development of mitochondrial-dependent adaptive processes in the myocardium was studied in vivo. The following parameters have been examined: (a) an urgent reaction of catalytic subunits of mitochondrial enzymes (NDUFV2, SDHA, Cyt b, COX2, ATP5A) in the myocardium as an indicator of the state of the respiratory chain electron transport function; (b) an urgent activation of signaling pathways dependent on GPR91, HIF-1α and VEGF, allowing us to assess their role in the formation of urgent mechanisms of adaptation to hypoxia in the myocardium; (c) changes in the ultrastructure of three subpopulations of myocardial mitochondria under these conditions. The studies were conducted on two rat phenotypes: rats with low resistance (LR) and high resistance (HR) to hypoxia. The adaptive and compensatory role of the mitochondrial complex II (MC II) in maintaining the electron transport and energy function of the myocardium in a wide range of reduced O₂ concentrations in the initial period of hypoxic exposure has been established. The features of urgent reciprocal regulatory interaction of NAD- and FAD-dependent oxidation pathways in myocardial mitochondria under these conditions have been revealed. The data indicating the participation of GPR91, HIF-1a and VEGF in this process have been obtained. The ultrastructure of the mitochondrial subpopulations in the myocardium of LR and HR rats differed in normoxic conditions and reacted differently to hypoxia of varying severity. The parameters studied together are highly informative indicators of the quality of cardiac activity and metabolic biomarkers of urgent adaptation in various hypoxic conditions. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptation to Hypoxia 2.0)

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15 pages, 3961 KiB

Open AccessArticle

Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention

by Kai-Chia Yeh, Chia-Jui Lee, Jen-Shin Song, Chien-Huang Wu, Teng-Kuang Yeh, Szu-Huei Wu, Tsung-Chin Hsieh, Yen-Ting Chen, Huan-Yi Tseng, Chen-Lung Huang, Chiung-Tong Chen, Jiing-Jyh Jan, Ming-Chen Chou, Kak-Shan Shia and Kuang-Hsing Chiang

Int. J. Mol. Sci. 2022, 23(19), 11730; https://doi.org/10.3390/ijms231911730 - 03 Oct 2022

Cited by 1 | Viewed by 1771

Abstract

CXCR4 antagonists have been claimed to reduce mortality after myocardial infarction in myocardial infarction (MI) animals, presumably due to suppressing inflammatory responses caused by myocardial ischemia-reperfusion injury, thus, subsequently facilitating tissue repair and cardiac function recovery. This study aims to determine whether a newly designed CXCR4 antagonist DBPR807 could exert better vascular-protective effects than other clinical counterparts (e.g., AMD3100) to alleviate cardiac damage further exacerbated by reperfusion. Consequently, we find that instead of traditional continuous treatment or multiple-dose treatment at different intervals of time, a single-dose treatment of DBPR807 before reperfusion in MI animals could attenuate inflammation via protecting oxidative stress damage and preserve vascular/capillary density and integrity via mobilizing endothelial progenitor cells, leading to a desirable fibrosis reduction and recovery of cardiac function, as evaluated with the LVEF (left ventricular ejection fraction) in infarcted hearts in rats and mini-pigs, respectively. Thus, it is highly suggested that CXCR4 antagonists should be given at a single high dose prior to reperfusion to provide the maximal cardiac functional improvement. Based on its favorable efficacy and safety profiles indicated in tested animals, DBPR807 has a great potential to serve as an adjunctive medicine for percutaneous coronary intervention (PCI) therapies in acute MI patients. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptation to Hypoxia 2.0)

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Review

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22 pages, 1527 KiB

Open AccessReview

Hypoxia and Intestinal Inflammation: Common Molecular Mechanisms and Signaling Pathways

by Kristina A. Dvornikova, Olga N. Platonova and Elena Y. Bystrova

Int. J. Mol. Sci. 2023, 24(3), 2425; https://doi.org/10.3390/ijms24032425 - 26 Jan 2023

Cited by 8 | Viewed by 2444

Abstract

The gastrointestinal tract (GI) has a unique oxygenation profile. It should be noted that the state of hypoxia can be characteristic of both normal and pathological conditions. Hypoxia-inducible factors (HIF) play a key role in mediating the response to hypoxia, and they are tightly regulated by a group of enzymes called HIF prolyl hydroxylases (PHD). In this review, we discuss the involvement of inflammation hypoxia and signaling pathways in the pathogenesis of inflammatory bowel disease (IBD) and elaborate in detail on the role of HIF in multiple immune reactions during intestinal inflammation. We emphasize the critical influence of tissue microenvironment and highlight the existence of overlapping functions and immune responses mediated by the same molecular mechanisms. Finally, we also provide an update on the development of corresponding therapeutic approaches that would be useful for treatment or prophylaxis of inflammatory bowel disease. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptation to Hypoxia 2.0)

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