Old and New Gasotransmitters in the Cardiovascular System: Focus on the Role of Nitric Oxide and Hydrogen Sulfide in Endothelial Cells and Cardiomyocytes

: There is considerable evidence in the heart that autophagy in cardiomyocytes is activated by hypoxia/reoxygenation (H/R) or in hearts by ischemia/reperfusion (I/R). Depending upon the experimental model and duration of ischemia, increases in autophagy in this setting maybe beneficial (cardioprotective) or deleterious (exacerbate I/R injury). Aside from the conundrum as to whether or not autophagy is an adaptive process, it is clearly regulated by a number of diverse molecules including reactive oxygen species (ROS), various kinases, hydrogen sulfide (H2S) and nitric oxide (NO). The purpose this review is to address briefly the controversy regarding the role of autophagy in this setting and to examine a variety of disparate molecules that are involved in its regulation.

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Hydrogen Sulfide Increases Nitric Oxide Production and Subsequent S-Nitrosylation in Endothelial Cells

The Scientific World JOURNAL ◽

10.1155/2014/480387 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Ping-Ho Chen ◽

Yaw-Syan Fu ◽

Yun-Ming Wang ◽

Kun-Han Yang ◽

Danny Ling Wang ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Hydrogen Sulfide ◽

Protein Kinase ◽

Fluorescent Probe ◽

Acid Methyl Ester ◽

High Specificity ◽

Protein S ◽

No Production ◽

No Donor

Hydrogen sulfide (H2S) and nitric oxide (NO), two endogenous gaseous molecules in endothelial cells, got increased attention with respect to their protective roles in the cardiovascular system. However, the details of the signaling pathways between H2S and NO in endothelia cells remain unclear. In this study, a treatment with NaHS profoundly increased the expression and the activity of endothelial nitric oxide synthase. Elevated gaseous NO levels were observed by a novel and specific fluorescent probe, 5-amino-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid methyl ester (FA-OMe), and quantified by flow cytometry. Further study indicated an increase of upstream regulator for eNOS activation, AMP-activated protein kinase (AMPK), and protein kinase B (Akt). By using a biotin switch, the level of NO-mediated protein S-nitrosylation was also enhanced. However, with the addition of the NO donor, NOC-18, the expressions of cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase were not changed. The level of H2S was also monitored by a new designed fluorescent probe, 4-nitro-7-thiocyanatobenz-2-oxa-1,3-diazole (NBD-SCN) with high specificity. Therefore, NO did not reciprocally increase the expression of H2S-generating enzymes and the H2S level. The present study provides an integrated insight of cellular responses to H2S and NO from protein expression to gaseous molecule generation, which indicates the upstream role of H2S in modulating NO production and protein S-nitrosylation.

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The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.586923 ◽

2020 ◽

Vol 10 ◽

Author(s):

Md. Aejazur Rahman ◽

Joel N. Glasgow ◽

Sajid Nadeem ◽

Vineel P. Reddy ◽

Ritesh R. Sevalkar ◽

...

Keyword(s):

Nitric Oxide ◽

Carbon Monoxide ◽

Hydrogen Sulfide ◽

Host Immunity ◽

Microbial Pathogens ◽

Microbial Pathogenesis ◽

Enzymatic Production ◽

Growth And Survival ◽

Wide Range

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

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