Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels

Miyamoto, Ryo; Koike, Sachiko; Takano, Yoko; Shibuya, Norihiro; Kimura, Yoshinobu; Hanaoka, Kenjiro; Urano, Yasuteru; Ogasawara, Yuki; Kimura, Hideo

doi:10.1038/srep45995

Cited by 110 publications

(102 citation statements)

References 41 publications

(75 reference statements)

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“…Thus HSNO can act a signaling molecule that may play a key role in cellular redox regulation [138]. Emerging data shows that the interaction between H 2 S and NO can also generate polysulfides (H 2 S n ; H 2 S 2 and H 2 S 3 ) [139]. In this study it was shown that H 2 S n generation was a fast reaction, and it activated transient receptor potential ankyrin 1 (TRPA1) channels in astrocytes and dorsal root ganglion (DRG) neurons, which can modify synaptic activity [140, 141].…”

Section: Interaction Between No and H2smentioning

confidence: 99%

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The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

Kashfi

2018

Biochemical Pharmacology

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Nitric oxide (NO) a gaseous free radical is one of the ten smallest molecules found in nature, while hydrogen sulfide (HS) is a gas that bears the pungent smell of rotten eggs. Both are toxic yet they are gasotransmitters of physiological relevance. There appears to be an uncanny resemblance between the general actions of these two gasotransmitters in health and disease. The role of NO and HS in cancer has been quite perplexing, as both tumor promotion and inflammatory activities as well as anti-tumor and antiinflammatory properties have been described. These paradoxes have been explained for both gasotransmitters in terms of each having a dual or biphasic effect that is dependent on the local flux of each gas. In this review/commentary, I have discussed the major roles of NO and HS in carcinogenesis, evaluating their dual nature, focusing on the enzymes that contribute to this paradox and evaluate the pros and cons of inhibiting or inducing each of these enzymes.

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Section: Interaction Between No and H2smentioning

confidence: 99%

“…H 2 S activates eNOS by an Akt-dependent phosphorylation of the protein [132]. NO can interact with H 2 S to form HSNO [138] and H 2 S n [139]; H 2 S can interact with NO 2 − [124] or with RSNO [147, 148] to produce NO. H 2 S decreases the sensitivity of the cGMP pathways and also it modifies K Ca channels to decrease their sensitivity to NO.…”

Section: Figurementioning

confidence: 99%

The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

Kashfi

2018

Biochemical Pharmacology

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“…Many antihypertensive drugs exert their protective effects at least in part by increasing NO bioavailability [15]. Deficiencies in H 2 S/NO may contribute to the development of hypertension, and in this context, combination therapy may prove fruitful in managing hypertension [8, 89, 243, 305]. …”

Section: Discussionmentioning

confidence: 99%

“…HSNO acid could freely diffuse through the membranes, acting as an NO carrier [244, 246]. HSNO acid could also react with hydrogen persulfide (HSSH) to produce SSNO − , which also can act as a NO carrier, leading to relaxation of VSM cells upon NO release [220, 243, 244]. In addition, HSNO is relatively unstable and in the presence of H 2 S and HSSH can produce nitroxyl (HNO) [220, 243, 244], which exerts vasorelaxatory effects by activation of cGMP-dependent [247] and independent [248] pathways.…”

Section: Interaction Between H2s and Nomentioning

confidence: 99%

Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension

Gheibi

Jeddi

Kashfi

et al. 2018

Biochemical Pharmacology

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Nitric oxide (NO) and hydrogen sulfide (HS) are two gasotransmitters that are produced in the vasculature and contribute to the regulation of vascular tone. NO and HS are synthesized in both vascular smooth muscle and endothelial cells; NO functions primarily through the sGC/cGMP pathway, and HS mainly through activation of the ATP-dependent potassium channels; both leading to relaxation of vascular smooth muscle cells. A deficit in the NO/HS homeostasis is involved in the pathogenesis of various cardiovascular diseases, especially hypertension. It is now becoming increasingly clear that there are important interactions between NO and HS and that have a profound impact on vascular tone and this may provide insights into the new therapeutic interventions. The aim of this review is to provide a better understanding of individual and interactive roles of NO and HS in vascular biology. Overall, available data indicate that both NO and HS contribute to vascular (patho)physiology and in regulating blood pressure. In addition, boosting NO and HS using various dietary sources or donors could be a hopeful therapeutic strategy in the management of hypertension.

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“…H 2 S plays synergistically with NO to form polysulfides (H 2 S n ) to act as TRPA1 channel activator in vasodilation [30]. Meanwhile, ZYZ-803, a slow-releasing H 2 S-NO hybrid molecule, could exert vasorelaxant effect [31] and angiogenesis [32] activity better than S-Propargyl-Cysteine (SPRC) and furoxan alone or together.…”

Section: Physiological Effects Of H2s and Related Molecular Mechanismmentioning

confidence: 99%

Atherosclerosis and the Hydrogen Sulfide Signaling Pathway – Therapeutic Approaches to Disease Prevention

Zj¹,

Wu²,

Guo³

et al. 2017

Cell Physiol Biochem

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Hydrogen sulfide (H₂S) is now admitted as a third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO), albeit it was originally considered as a foul and poisonous gas. Endogenous H₂S production in mammalian cells is counting on the three enzymes acting on cysteine. Involvement of H₂S in various physiological and pathological processes has been extensively studied in the last fifteen years. Mounting evidence suggests that H₂S is able to protect against atherosclerosis development and progression. Exogenous H₂S supplement has salutary effects on atherogenesis, and reduction of the endogenous H₂S level accelerates atherosclerosis. The anti-atherosclerotic mechanisms of H₂S have been descried in different aspects, including endothelium preservation, antioxidative action, anti-inflammatory responses, vasorelaxation, regulation of ion channels, etc. However, further investigation is still needed to help us gain more insights into the fundamental underlying mechanisms, and that will allow us to design better therapeutic applications of H₂S in the treatment of atherosclerosis.

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Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels

Cited by 110 publications

References 41 publications

The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension

Atherosclerosis and the Hydrogen Sulfide Signaling Pathway – Therapeutic Approaches to Disease Prevention

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