Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed

2012 ◽  
Vol 92 (2) ◽  
pp. 791-896 ◽  
Author(s):  
Rui Wang
Keyword(s):  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Erectile Dysfunction ◽  
Mammalian Cells ◽  
New Technologies ◽  
Molecular Targets ◽  
Signaling Proteins ◽  
Physiological Functions ◽  
Physiological Importance

The important life-supporting role of hydrogen sulfide (H2S) has evolved from bacteria to plants, invertebrates, vertebrates, and finally to mammals. Over the centuries, however, H2S had only been known for its toxicity and environmental hazard. Physiological importance of H2S has been appreciated for about a decade. It started by the discovery of endogenous H2S production in mammalian cells and gained momentum by typifying this gasotransmitter with a variety of physiological functions. The H2S-catalyzing enzymes are differentially expressed in cardiovascular, neuronal, immune, renal, respiratory, gastrointestinal, reproductive, liver, and endocrine systems and affect the functions of these systems through the production of H2S. The physiological functions of H2S are mediated by different molecular targets, such as different ion channels and signaling proteins. Alternations of H2S metabolism lead to an array of pathological disturbances in the form of hypertension, atherosclerosis, heart failure, diabetes, cirrhosis, inflammation, sepsis, neurodegenerative disease, erectile dysfunction, and asthma, to name a few. Many new technologies have been developed to detect endogenous H2S production, and novel H2S-delivery compounds have been invented to aid therapeutic intervention of diseases related to abnormal H2S metabolism. While acknowledging the challenges ahead, research on H2S physiology and medicine is entering an exponential exploration era.

scholarly journals The production and role of hydrogen sulfide and hydrogen polysulfides in mammalian cells

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO4-1-23
Author(s):  
Norihiro Shibuya ◽  
Shin Koike ◽  
Ryo Miyamoto ◽  
Yuka Kimura ◽  
Kenjiro Hanaoka ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Mammalian Cells

Overview of potential molecular targets for hydrogen sulfide: A new strategy for treating erectile dysfunction

Nitric Oxide ◽  
2015 ◽  
Vol 50 ◽  
pp. 65-78 ◽  
Author(s):  
Serap Gur ◽  
Philip J. Kadowitz ◽  
Suresh C. Sikka ◽  
Taylor C. Peak ◽  
Wayne J.G. Hellstrom
Keyword(s):  
Hydrogen Sulfide ◽  
Erectile Dysfunction ◽  
Molecular Targets ◽  
New Strategy

scholarly journals Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology

2018 ◽  
Vol 2018 ◽  
pp. 1-31 ◽  
Author(s):  
Alessandro Giuffrè ◽  
João B. Vicente
Keyword(s):  
Hydrogen Sulfide ◽  
Mammalian Cells ◽  
Protein Targets ◽  
Metal Centers ◽  
Cellular Processes ◽  
Signaling Function ◽  
Enzymatic Systems ◽  
Bona Fide ◽  
Different Levels

Hydrogen sulfide (H2S) has emerged as a relevant signaling molecule in physiology, taking its seat as a bona fide gasotransmitter akin to nitric oxide (NO) and carbon monoxide (CO). After being merely regarded as a toxic poisonous molecule, it is now recognized that mammalian cells are equipped with sophisticated enzymatic systems for H2S production and breakdown. The signaling role of H2S is mainly related to its ability to modify different protein targets, particularly by promoting persulfidation of protein cysteine residues and by interacting with metal centers, mostly hemes. H2S has been shown to regulate a myriad of cellular processes with multiple physiological consequences. As such, dysfunctional H2S metabolism is increasingly implicated in different pathologies, from cardiovascular and neurodegenerative diseases to cancer. As a highly diffusible reactive species, the intra- and extracellular levels of H2S have to be kept under tight control and, accordingly, regulation of H2S metabolism occurs at different levels. Interestingly, even though H2S, NO, and CO have similar modes of action and parallel regulatory targets or precisely because of that, there is increasing evidence of a crosstalk between the three gasotransmitters. Herein are reviewed the biochemistry, metabolism, and signaling function of hydrogen sulfide, as well as its interplay with the other gasotransmitters, NO and CO.

scholarly journals Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding

2020 ◽  
Vol 295 (32) ◽  
pp. 11161-11173 ◽  
Author(s):  
Yasmin A. Kadry ◽  
Eesha M. Maisuria ◽  
Clotilde Huet-Calderwood ◽  
David A. Calderwood
Keyword(s):  
Mammalian Cells ◽  
Point Mutations ◽  
Focal Adhesions ◽  
Comparative Sequence Analysis ◽  
Signaling Proteins ◽  
Binding Assays ◽  
Physiological Importance ◽  
Self Association ◽  
Complex Signaling ◽  
Extracellular Environment

The integrin family of transmembrane adhesion receptors coordinates complex signaling networks that control the ability of cells to sense and communicate with the extracellular environment. Kindlin proteins are a central cytoplasmic component of these networks, directly binding integrin cytoplasmic domains and mediating interactions with cytoskeletal and signaling proteins. The physiological importance of kindlins is well established, but how the scaffolding functions of kindlins are regulated at the molecular level is still unclear. Here, using a combination of GFP nanotrap association assays, pulldown and integrin-binding assays, and live-cell imaging, we demonstrate that full-length kindlins can oligomerize (self-associate) in mammalian cells, and we propose that this self-association inhibits integrin binding and kindlin localization to focal adhesions. We show that both kindlin-2 and kindlin-3 can self-associate and that kindlin-3 self-association is more robust. Using chimeric mapping, we demonstrate that the F2PH and F3 subdomains are important for kindlin self-association. Through comparative sequence analysis of kindlin-2 and kindlin-3, we identify kindlin-3 point mutations that decrease self-association and enhance integrin binding, affording mutant kindlin-3 the ability to localize to focal adhesions. Our results support the notion that kindlin self-association negatively regulates integrin binding.

Immuno-metabolic interfaces in cardiac disease and failure

2021 ◽  
Author(s):  
Edoardo Bertero ◽  
Jan Dudek ◽  
Clement Cochain ◽  
Murilo Delgobo ◽  
Gustavo Ramos ◽  
...  
Keyword(s):  
Heart Failure ◽  
New Technologies ◽  
Cell Function ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Cardiac Metabolism ◽  
Special Focus ◽  
Therapeutic Approaches ◽  
System Metabolism

Abstract The interplay between the cardiovascular system, metabolism, and inflammation plays a central role in the pathophysiology of a wide spectrum of cardiovascular diseases, including heart failure. Here, we provide an overview of the fundamental aspects of the interrelation between inflammation and metabolism, ranging from the role of metabolism in immune cell function to the processes how inflammation modulates systemic and cardiac metabolism. Furthermore, we discuss how disruption of this immuno-metabolic interface is involved in the development and progression of cardiovascular disease, with a special focus on heart failure. Finally, we present new technologies and therapeutic approaches that have recently emerged and hold promise for the future of cardiovascular medicine.

scholarly journals Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

2016 ◽  
Vol 310 (7) ◽  
pp. H802-H812 ◽  
Author(s):  
Bryan T. Hackfort ◽  
Paras K. Mishra
Keyword(s):  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
High Dose ◽  
Physiological Level ◽  
Cellular Processes ◽  
Regulatory Rnas ◽  
Apoptosis And Inflammation

Despite an obnoxious smell and toxicity at a high dose, hydrogen sulfide (H2S) is emerging as a cardioprotective gasotransmitter. H2S mitigates pathological cardiac remodeling by regulating several cellular processes including fibrosis, hypertrophy, apoptosis, and inflammation. These encouraging findings in rodents led to initiation of a clinical trial using a H2S donor in heart failure patients. However, the underlying molecular mechanisms by which H2S mitigates cardiac remodeling are not completely understood. Empirical evidence suggest that H2S may regulate signaling pathways either by directly influencing a gene in the cascade or interacting with nitric oxide (another cardioprotective gasotransmitter) or both. Recent studies revealed that H2S may ameliorate cardiac dysfunction by up- or downregulating specific microRNAs. MicroRNAs are noncoding, conserved, regulatory RNAs that modulate gene expression mostly by translational inhibition and are emerging as a therapeutic target for cardiovascular disease (CVD). Few microRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new avenue for exploring the H2S-microRNA crosstalk in CVD. This review embodies regulatory mechanisms that maintain the physiological level of H2S, exogenous H2S donors used for increasing the tissue levels of H2S, H2S-mediated regulation of CVD, H2S-microRNAs crosstalk in relation to the pathophysiology of heart disease, clinical trials on H2S, and future perspectives for H2S as a therapeutic agent for heart failure.

scholarly journals Emerging Molecular Pathways Involved in Pathophysiology of Cardiac Remodeling

2021 ◽  
Vol 11 (2) ◽  
pp. 178-187
Author(s):  
Sunny Dhiman ◽  
Priyankul Palia ◽  
Pankaj Kumar ◽  
Shalini Jamwal ◽  
Chinu Kumari
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Morphological Changes ◽  
Molecular Targets ◽  
Molecular Pathways ◽  
Specific Intervention ◽  
Experimental Findings ◽  
Molecular Components ◽  
Pumping Function

Mammalian heart is a dynamic organ that can adapt morphological changes in response to alteration in workload. Various clinical and experimental findings revealed that in response to physiological stimuli or pathological insults, the heart undergoes cardiac remodeling which can be characterized by molecular, cellular or interstitial changes and can be manifested clinically as changes in size, shape and pumping function of the heart. A Sound understanding of changes in hearts cellular and molecular components and to mediators that derive homeostatic control is necessary before a specific intervention is pursued. Summarized data of this review comprises role of various novel emerging molecular pathways involvement in the pathophysiology of cardiac remodeling. Keywords: Cardiac remodeling, hypertrophy, protein kinase, heart failure, molecular targets, pathological insult.

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