Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress

Bearden, Shawn E.; Beard, Richard S.; Pfau, Jean C.

doi:10.1152/ajpheart.00555.2010

Cited by 85 publications

(56 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with the reduced H 2 S levels, homocysteine levels were lower in MsrA -/ -than in MsrA + / + mice. Recently, Bearden et al reported that extracellular trans-sulfuration from homocysteine to H 2 S protects the endothelium against redox stress (2). Our data suggest that MsrA deficiency alters methionine metabolism and results in reduced homocysteine levels, leading to a sequential reduction in H 2 S production.…”

Section: Fig 5 Levels Of H 2 S In Plasma (A) and Kidneys (B)supporting

confidence: 50%

Protective Role of Methionine Sulfoxide Reductase a Against Ischemia/Reperfusion Injury in Mouse Kidney and Its Involvement in the Regulation of Transsulfuration Pathway

Kim

Choi

Jung

et al. 2013

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Aims: Methionine sulfoxide reductase A (MsrA) and methionine metabolism are associated with oxidative stress, a principal cause of ischemia/reperfusion (I/R) injury. Herein, we investigated the protective role of MsrA against kidney I/R injury and the involvement of MsrA in methionine metabolism and the transsulfuration pathway during I/R. Results: We found that MsrA gene-deleted mice (MsrA -/ -) were more susceptible to kidney I/R injury than wild-type mice (MsrA +/+ ). Deletion of MsrA enhanced renal functional and morphological impairments, congestion, inflammatory responses, and oxidative stress under I/R conditions. Concentrations of homocysteine and H 2 S in the plasma of control MsrA -/ -mice were significantly lower than those in control MsrA +/+ mice. I/R reduced the levels of homocysteine and H 2 S in both MsrA +/+ and MsrA -/ -mice, and these reductions were significantly more profound in MsrA -/ -than in MsrA +/+ mice. I/R reduced the expression and activities of cystathionine-b-synthase (CBS) and cystathionine-c-lyase (CSE), both of which are H 2 S-producing enzymes, in the kidneys. These reductions were more profound in the MsrA -/ -mice than in the MsrA +/+ mice. Innovation: The data provided herein constitute the first in vivo evidence for the involvement of MsrA in regulating methionine metabolism and the trans-sulfuration pathway under normal and I/R conditions. Conclusion: Our data demonstrate that MsrA protects the kidney against I/R injury, and that this protection is associated with reduced oxidative stress and inflammatory responses. The data indicate that MsrA regulates H 2 S production during I/R by modulating the expression and activity of the CBS and CSE enzymes.

show abstract

Section: Fig 5 Levels Of H 2 S In Plasma (A) and Kidneys (B)supporting

confidence: 50%

Protective Role of Methionine Sulfoxide Reductase a Against Ischemia/Reperfusion Injury in Mouse Kidney and Its Involvement in the Regulation of Transsulfuration Pathway

Kim

Choi

Jung

et al. 2013

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…This was perhaps one of the mechanisms underlying the H 2 S inhibition of pulmonary arterial remodeling in vivo. As previously demonstrated, H 2 S can also inhibit arterial remodeling by endothelial protection (37) and the induction of the apoptosis of smooth muscle cells (38). In the current study, we mainly investigated the effects of H 2 S on cell proliferation and the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 88%

H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2

Liu

Cai

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main cause of pulmonary arterial hypertension (PAH), in which oxidative stress, cyclooxygenase (COX)-2 and hydrogen sulfide (H 2 S) all play an important role. In the present study, we aimed to examine the effects of H 2 S on the hypoxia-induced proliferation of human PASMCs (HPASMCs) and to elucidate the underlying mechanisms. The HPASMCs were treated with cobalt chloride (CoCl 2 ), a hypoxia-mimicking agent, to establish a cellular model of hypoxic PAH. Prior to treatment with CoCl 2 , the cells were pre-conditioned with sodium hydrosulfide (NaHS), a donor of H 2 S. Cell proliferation, reactive oxygen species (ROS) production, COX-2 expression, prostacyclin (also known as prostaglandin I2 or PGI 2 ) secretion and H 2 S levels were detected in the cells. The exposure of the HPASMCs to CoCl 2 markedly increased cell proliferation, accompanied by a decrease in COX-2 expression, PGI 2 secretion and H 2 S levels; however, the levels of ROS were not altered. Although the exogenous ROS donor, H 2 O 2 , triggered similar degrees of proliferation to CoCl 2 , the ROS scavenger, N-acetyl-L-cysteine (NAC), markedly abolished the H 2 O 2 -induced cell proliferation, as opposed to the CoCl 2 -induced proliferation. The CoCl 2 -induced proliferation of HPASMCs was suppressed by exogenously applied PGI 2 . The addition of H 2 S (NaHS) attenuated the CoCl 2 -induced cell proliferation through the increase in the intercellular content of H 2 S. Importantly, the exposure of the cells to H 2 S suppressed the CoCl 2 -induced downregulation in COX-2 expression and PGI 2 secretion from the HPASMCs. In conclusion, the results from the current study suggest that H 2 S inhibits hypoxia-induced cell proliferation through the upregulation of COX-2/PGI 2 , as opposed to ROS.

show abstract

“…Hypoxia appears to increase CBS in the mitochondria (164) and stress-related stimuli can translocate CSE to the mitochondria, although this may take hours (42); additional details are provided in sections ''CBS Translocation to Mitochondria'' and ''CSE Translocation to Mitochondria.'' Initially, it was believed that CBS was predominantly found in the brain and CSE was found in the cardiovascular system [reviewed in Kimura (73)], although a broader distribution is now becoming apparent (6,73,129). H 2 S can also be derived from d-cysteine; however, this appears limited to the brain and kidney, where it protects the former from oxidative stress and the latter from re-perfusion injury (147).…”

Section: Metabolic Relationships Between H 2 S and Omentioning

confidence: 99%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Significance: Although oxygen (O 2 )-sensing cells and tissues have been known for decades, the identity of the O 2 -sensing mechanism has remained elusive. Evidence is accumulating that O 2 -dependent metabolism of hydrogen sulfide (H 2 S) is this enigmatic O 2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H 2 S synthesis and metabolism have shown that reciprocal H 2 S/O 2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O 2 controls H 2 S inactivation, and the effects of H 2 S on downstream signaling events are consistent with those activated by hypoxia. H 2 S-mediated O 2 sensing has been demonstrated in a variety of O 2 -sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H 2 S and its metabolites. Future Directions: Development of specific inhibitors of H 2 S metabolism and effector activation as well as cellular organelle-targeted compounds that release H 2 S in a timeor environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377-397.

show abstract

Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress

Abstract: Bearden SE, Beard RS Jr, Pfau JC. Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress.

Cited by 85 publications

References 45 publications

Protective Role of Methionine Sulfoxide Reductase a Against Ischemia/Reperfusion Injury in Mouse Kidney and Its Involvement in the Regulation of Transsulfuration Pathway

Protective Role of Methionine Sulfoxide Reductase a Against Ischemia/Reperfusion Injury in Mouse Kidney and Its Involvement in the Regulation of Transsulfuration Pathway

H2S inhibition of chemical hypoxia-induced proliferation of HPASMCs is mediated by the upregulation of COX-2/PGI2

Hydrogen sulfide as an oxygen sensor

Contact Info

Product

Resources

About