Cystathionine β-synthase regulates endothelial function via protein S-sulfhydration
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...Taken together, these findings suggest that CBS deficiency will contribute to endothelial dysfunction by decreasing H2S-induced vascular relaxation [101,104]....
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Cites background from "Cystathionine β-synthase regulates ..."
...Persulfidationof these residues stabilizes SP1and regulates its transcription ofVEGF receptor 2 andneurolipin-1, 2major regulators of endothelial cell function (140)....
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...Moreover, our grouphas shown that persulfidation of SP1 by H2S can enhance its transcriptional activity, thereby indicating a potential mechanism by which HDmay be treated by H2S (140)....
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References
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"Cystathionine β-synthase regulates ..." refers background in this paper
...To determine how CBS regulates EC function, we focused on the VEGF/VEGFR-2 signaling axis, arguably the predominant pathway responsible for EC proliferation, migration, and survival (28)....
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"Cystathionine β-synthase regulates ..." refers background in this paper
...Although theobservations reportedare suggestive of a causal role for Hcy in endothelial dysfunction, clinical trials using vitamin supplementation though lowered Hcy levels did not alter disease outcome (13, 14)....
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...However, clinical trials using vitamin supplements lowered Hcy but did not alter disease outcome, suggesting an intricate involvement of metabolites generated through the transsulfuration pathway in causing endothelial dysfunction (13, 14)....
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"Cystathionine β-synthase regulates ..." refers background or methods in this paper
...In conclusion, our work emphasizes the importance of CBS-mediated protein S-sulfhydration in maintaining vascular health and function and purports possible H2Sdonor based therapies for treatment of endothelial dysfunction in CBS deficiency....
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...Sulfhydration stabilizes and enhances binding of SP1 to the VEGFR-2 promoter Given thatH2S canmodify proteins through S-sulfhydration (24), we performed themaleimide assay in which the -SH and -SSH groups but not S-S in a protein react with fluorescentmaleimide (27) (Fig....
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...A few significant proteins have recently been identified to be targets of protein S-sulfhydration, including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), actin, tubulin, NF-kB, Parkin, andCa2+-TRP channels (23, 25–27)....
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...Using the modified biotin-switch assay (23), we then determined if Sp1 could be sulfhydratedbyNaHS....
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...Recent studies have demonstrated that H2S functions by modifying free thiol groups (-SH) in a protein to form persulfides (-SSH), a process known as protein S-sulfhydration (23, 24)....
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