Hydrogen Sulfide and Diseases

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 20561

Special Issue Editor


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Guest Editor
1. School of Pharmacy and State Key Lab. of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China
2. Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
Interests: inflammation; immune response; hydrogen sulfide; molecular mechanisms; drug discovery, natural product research, pharmacology
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Special Issue Information

Dear Colleagues,

Hydrogen sulfide (H2S), traditionally known as a toxic gas but more recently as a third gaseous signal transmitter in humans, plays an important role in the development of cardiovascular diseases (CVD) through mechanisms such as angiogenesis, vasodilation, antivascular endothelial cell senescence, etc. H2S has been reported for the treatment of neurological disorders, gastrointestinal diseases, renal dysfunctions, cancers and even erectile dysfunction. H2S has also been recognized in treating inflammatory disease and regulating the immune system, with extensive solid studies. The multiple molecular targets of H2S have shown wide therapeutic applications, via transcription factors and membrane ion channels binding to various proteins and/or enzymes though novel molecular mechanisms which are slowly beginning to be understood. The multifunctional regulations of H2S, which act as inalienable cross-talk in the progress of several diseases, have opened up a new avenue for the study of basic and clinical development mechanisms and H2S-related drug discoveries. Recently, novel H2S donors have been explored and synthesized that are able to release H2S in a control-released manner.

The current Special Issue will focus on the latest development of physiological, pathophysiological and therapeutical effects of H2S in different diseases, and may provide a prognosis on whether H2S donors are a new member of the first-in-class drug’s family.

Prof. Dr. Yi Zhun Zhu
Guest Editor

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Keywords

  • hydrogen sulfide
  • gaseous signal transmitter
  • therapeutic effects
  • diseases

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Published Papers (8 papers)

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Research

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17 pages, 3853 KiB  
Article
S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
by Haiyan Xi, Chenye Wang, Qixiu Li, Qing Ye, Yizhun Zhu and Yicheng Mao
Antioxidants 2023, 12(2), 294; https://doi.org/10.3390/antiox12020294 - 28 Jan 2023
Cited by 2 | Viewed by 1995
Abstract
Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H2S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and [...] Read more.
Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H2S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and to explore the potential mechanisms. The effects and mechanisms of SPRC on angiogenesis and peripheral nerve repair were examined under hypoxic condition by establishing a sciatic nerve crushed injury model in mice and rats, and a hypoxia model in human umbilical vascular endothelial cells (HUVECs) in vitro. We found that SPRC accelerated the function recovery of the injured sciatic nerve and alleviated atrophy of the gastrocnemius muscle in mice. It facilitated the viability of Schwann cells (SCs), the outgrowth and myelination of regenerated axons, and angiogenesis in rats. It enhanced the viability, proliferation, adhesion, migration, and tube formation of HUVECs under hypoxic condition. SPRC activated sirtuin1 (SIRT1) expression by promoting the production of endogenous H2S, and SIRT1 negatively regulated Notch signaling in endothelial cells (ECs), thereby promoting angiogenesis. Collectively, our study has provided important evidence that SPRC has an effective role in peripheral nerve repair through microvascular reconstruction, which could be a potentially effective medical therapy for peripheral nerve injury. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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18 pages, 4675 KiB  
Article
The Inhibitory Role of Hydrogen Sulfide in UII-Induced Cardiovascular Effects and the Underlying Signaling Pathways
by Na-Na Zhang, Hai-Yan Xu, Xiao-Ni Liu, Yi-Fan Chen, Chun-Mei Xia, Xing-Zhong Wu and Ning Lu
Antioxidants 2022, 11(11), 2253; https://doi.org/10.3390/antiox11112253 - 15 Nov 2022
Cited by 2 | Viewed by 1824
Abstract
Urotensin II (UII) could increase blood pressure and heart rate via increased central reactive oxygen species (ROS) levels. We reported previously that hydrogen sulfide (H2S) exerts an antihypertensive effect by suppressing ROS production. The aim of the current study is to [...] Read more.
Urotensin II (UII) could increase blood pressure and heart rate via increased central reactive oxygen species (ROS) levels. We reported previously that hydrogen sulfide (H2S) exerts an antihypertensive effect by suppressing ROS production. The aim of the current study is to further examine the effects of endogenous and exogenous H2S on UII-induced cardiovascular effects by using an integrated physiology approach. We also use cell culture and molecular biological techniques to explore the inhibitory role of H2S on UII-induced cardiovascular effects. In this study, we found that cystathionine-β-synthase (CBS), the main H2S synthesizing enzyme in CNS, was expressed in neuronal cells of the rostral ventrolateral medulla (RVLM) area. Cellular distribution of CBS and urotensin II receptor (UT) in SH-SY5Y cells that are confirmed as glutamatergic were identified by immunofluorescent and Western blots assay. In Sprague–Dawley rats, administration of UII into the RVLM resulted in an increase in mean arterial pressure (MAP), heart rate (HR), ROS production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and phosphorylation of p47phox, extracellular signal-regulated protein kinase (ERK)1/2 and p38MAPK, but not stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK). These effects of UII were attenuated by application into the RVLM of endogenous (L-cysteine, SAM) or exogenous (NaHS) H2S. These results were confirmed in SH-SY5Y cells. UII-induced cardiovascular effects were also significantly abolished by pretreatment with microinjection of Tempol, Apocynin, SB203580, or PD98059 into the RVLM. Preincubated SH-SY5Y cells with Apocynin before administration of UII followed by Western blots assay showed that ROS is in the upstream of p38MAPK/ERK1/2. Gao activation assay in SH-SY5Y cells suggested that H2S may exert an inhibitory role on UII-induced cardiovascular effects by inhibiting the activity of Gαo. These results suggest that both endogenous and exogenous H2S attenuate UII-induced cardiovascular effects via Gαo-ROS-p38MAPK/ERK1/2 pathway. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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17 pages, 8203 KiB  
Article
Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches
by Yoo Lim Chun, Won-Joon Eom, Jun Hyung Lee, Thy N. C. Nguyen, Ki-Hoon Park, Hyung-Joo Chung, Han Seo, Youngbuhm Huh, Sang Hoon Kim, Seung Geun Yeo, Wonseok Park, Geul Bang, Jin Young Kim, Min-Sik Kim, Na Young Jeong and Junyang Jung
Antioxidants 2022, 11(8), 1606; https://doi.org/10.3390/antiox11081606 - 19 Aug 2022
Cited by 3 | Viewed by 2761
Abstract
N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H2S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H2S [...] Read more.
N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H2S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H2S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing (RNA-seq)) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxidative stress were transcriptionally regulated by several transcription factors, such as Atf3, Fos, Rela, and Smad2. In a functional enrichment analysis, cell cycle, oxidative stress, and lipid/cholesterol metabolism were enriched, implicating H2S signaling in Schwann cell dedifferentiation, proliferation, and myelination. NEM-induced changes in the H2S signaling pathway affect oxidative stress, lipid metabolism, and the cell cycle in Schwann cells. Therefore, regulation of the H2S signaling pathway by NEM during PND could prevent Schwann cell demyelination, dedifferentiation, and proliferation. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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Review

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17 pages, 635 KiB  
Review
The Impact of Drugs on Hydrogen Sulfide Homeostasis in Mammals
by Asrar Alsaeedi, Simon Welham, Peter Rose and Yi-Zhun Zhu
Antioxidants 2023, 12(4), 908; https://doi.org/10.3390/antiox12040908 - 11 Apr 2023
Cited by 8 | Viewed by 2507
Abstract
Mammalian cells and tissues have the capacity to generate hydrogen sulfide gas (H2S) via catabolic routes involving cysteine metabolism. H2S acts on cell signaling cascades that are necessary in many biochemical and physiological roles important in the heart, brain, [...] Read more.
Mammalian cells and tissues have the capacity to generate hydrogen sulfide gas (H2S) via catabolic routes involving cysteine metabolism. H2S acts on cell signaling cascades that are necessary in many biochemical and physiological roles important in the heart, brain, liver, kidney, urogenital tract, and cardiovascular and immune systems of mammals. Diminished levels of this molecule are observed in several pathophysiological conditions including heart disease, diabetes, obesity, and immune function. Interestingly, in the last two decades, it has become apparent that some commonly prescribed pharmacological drugs can impact the expression and activities of enzymes responsible for hydrogen sulfide production in cells and tissues. Therefore, the current review provides an overview of the studies that catalogue key drugs and their impact on hydrogen sulfide production in mammals. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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17 pages, 1859 KiB  
Review
The Role of Hydrogen Sulfide in Plaque Stability
by Qian Lin and Bin Geng
Antioxidants 2022, 11(12), 2356; https://doi.org/10.3390/antiox11122356 - 28 Nov 2022
Cited by 8 | Viewed by 2996
Abstract
Atherosclerosis is the greatest contributor to cardiovascular events and is involved in the majority of deaths worldwide. Plaque rapture or erosion precipitates life-threatening thrombi, resulting in the obstruction blood flow to the heart (acute coronary syndrome), brain (ischemic stroke) or low extremities (peripheral [...] Read more.
Atherosclerosis is the greatest contributor to cardiovascular events and is involved in the majority of deaths worldwide. Plaque rapture or erosion precipitates life-threatening thrombi, resulting in the obstruction blood flow to the heart (acute coronary syndrome), brain (ischemic stroke) or low extremities (peripheral vascular diseases). Among these events, major causation dues to the plaque rupture. Although the initiation, procession, and precise time of controlling plaque rupture are unclear, foam cell formation and apoptosis, cell death, extracellular matrix components, protease expression and activity, local inflammation, intraplaque hemorrhage, and calcification contribute to the plaque instability. These alterations tightly associate with the function regulation of intraplaque various cell populations. Hydrogen sulfide (H2S) is gasotransmitter derived from methionine metabolism and exerts a protective role in the genesis of atherosclerosis. Recent progress also showed H2S mediated the plaque stability. In this review, we discuss the progress of endogenous H2S modulation on functions of vascular smooth muscle cells, monocytes/macrophages, and T cells, and the molecular mechanism in plaque stability. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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21 pages, 1185 KiB  
Review
Hydrogen Sulfide: A Gaseous Mediator and Its Key Role in Programmed Cell Death, Oxidative Stress, Inflammation and Pulmonary Disease
by Zhixing Zhu, Xihua Lian and Madhav Bhatia
Antioxidants 2022, 11(11), 2162; https://doi.org/10.3390/antiox11112162 - 31 Oct 2022
Cited by 11 | Viewed by 2263
Abstract
Hydrogen sulfide (H2S) has been acknowledged as a novel gaseous mediator. The metabolism of H2S in mammals is tightly controlled and is mainly achieved by many physiological reactions catalyzed by a suite of enzymes. Although the precise actions of [...] Read more.
Hydrogen sulfide (H2S) has been acknowledged as a novel gaseous mediator. The metabolism of H2S in mammals is tightly controlled and is mainly achieved by many physiological reactions catalyzed by a suite of enzymes. Although the precise actions of H2S in regulating programmed cell death, oxidative stress and inflammation are yet to be fully understood, it is becoming increasingly clear that H2S is extensively involved in these crucial processes. Since programmed cell death, oxidative stress and inflammation have been demonstrated as three important mechanisms participating in the pathogenesis of various pulmonary diseases, it can be inferred that aberrant H2S metabolism also functions as a critical contributor to pulmonary diseases, which has also been extensively investigated. In the meantime, substantial attention has been paid to developing therapeutic approaches targeting H2S for pulmonary diseases. In this review, we summarize the cutting-edge knowledge on the metabolism of H2S and the relevance of H2S to programmed cell death, oxidative stress and inflammation. We also provide an update on the crucial roles played by H2S in the pathogenesis of several pulmonary diseases. Finally, we discuss the perspective on targeting H2S metabolism in the treatment of pulmonary diseases. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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18 pages, 1672 KiB  
Review
Hydrogen Sulfide Biomedical Research in China—20 Years of Hindsight
by Rui Wang and Chaoshu Tang
Antioxidants 2022, 11(11), 2136; https://doi.org/10.3390/antiox11112136 - 28 Oct 2022
Cited by 7 | Viewed by 1951
Abstract
Hydrogen sulfide (H2S) is an important gasotransmitter that is produced by mammalian cells and performs profound physiological and pathophysiological functions. Biomedical research on H2S metabolism and function in China began 20 years ago, which pioneered the examination of the [...] Read more.
Hydrogen sulfide (H2S) is an important gasotransmitter that is produced by mammalian cells and performs profound physiological and pathophysiological functions. Biomedical research on H2S metabolism and function in China began 20 years ago, which pioneered the examination of the correlation of abnormal H2S metabolism and cardiovascular diseases. Over the last two decades, research teams in China have made numerous breakthrough discoveries on the effects of H2S metabolism on hypertension, atherosclerosis, pulmonary hypertension, shock, angiogenesis, chronic obstructive pulmonary disease, pain, iron homeostasis, and testicle function, to name a few. These research developments, carried by numerous research teams all over China, build nationwide research network and advance both laboratory study and clinical applications. An integrated and collaborative research strategy would further promote and sustain H2S biomedical research in China and in the world. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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16 pages, 827 KiB  
Review
The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis
by Thi Thuy Tien Vo, Thao Duy Huynh, Ching-Shuen Wang, Kuei-Hung Lai, Zih-Chan Lin, Wei-Ning Lin, Yuh-Lien Chen, Tzu-Yu Peng, Ho-Cheng Wu and I-Ta Lee
Antioxidants 2022, 11(8), 1619; https://doi.org/10.3390/antiox11081619 - 20 Aug 2022
Cited by 12 | Viewed by 3216
Abstract
The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed [...] Read more.
The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism. Full article
(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)
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