{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T03:59:31Z","timestamp":1754193571958,"version":"3.41.2"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. Previous studies have found that disorders of cystathionine-gamma-lyase\/hydrogen sulfide (CSE\/H<jats:sub>2<\/jats:sub>S) system in maintenance hemodialysis patients are correlated with the risk of cardiovascular disease. Although the role of CSE\/H<jats:sub>2<\/jats:sub>S system in UAAS has been preliminarily explored, the molecular mechanism of CSE\/H<jats:sub>2<\/jats:sub>S is still not systematically elaborated, and the molecular mechanism of nPKC\u03b4 and its related signaling pathway in UAAS is still not thoroughly studied.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Forty chronic kidney disease (CHD) patients were studied and the activation of nPKC\u03b4 in peripheral blood mononuclear cells (PBMCs) were detected. ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice aged 6 weeks were treated with 5\/6 nephrectomy and high-fat diet to make UAAS model. They were divided into Sham group (Sham group), UAAS group (UAAS group), UAAS+L-cysteine group (UAAS+L-cys group), UAAS+sodium hydrosulfide group (UAAS+NaHS group) and UAAS+propargylglycine group (UAAS+PPG group). The UAAS+L-cys group, UAAS+NaHS group and UAAS+PPG group were respectively given L-cys, NaHS and PPG by intraperitoneal injection. The aorta was taken 6 weeks after surgery. Western blot was used to detect the activation of nPKC\u03b4, the phosphorylation of Akt, and the expression of VCAM-1 in the aorta of mice.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The membrane translocation of nPKC\u03b4 in CHD patients with plaque was higher than that in CHD patients without plaque. The membrane translocation of nPKC\u03b4 and the expression of VCAM-1 in UAAS group was higher than sham group, L-cys or NaHS injection could suppress the membrane translocation of nPKC\u03b4 and the expression of VCAM-1, but PPG treatment resulted in more membrane translocation of nPKC\u03b4 and the expression of VCAM-1 (<jats:italic>P<\/jats:italic>&amp;lt;0.05, n=6 per group). Akt phosphorylation in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation, but PPG treatment resulted in more decrease in the Akt phosphorylation (<jats:italic>P<\/jats:italic>&amp;lt;0.05, n=6 per group).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Endogenous CSE\/H<jats:sub>2<\/jats:sub>S system protected against the formation of UAAS via nPKC\u03b4\/Akt signal pathway. The imbalance of CSE\/H<jats:sub>2<\/jats:sub>S system may participate in the formation of UAAS by affecting the expression of downstream molecule VCAM-1, which may be mediated by nPKC\u03b4\/Akt signaling pathway.<\/jats:p>","DOI":"10.3389\/fmolb.2020.615816","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T18:47:21Z","timestamp":1612982841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Hydrogen Sulfide Protects Against Uremic Accelerated Atherosclerosis via nPKC\u03b4\/Akt Signal Pathway"],"prefix":"10.3389","volume":"7","author":[{"given":"Xiangxue","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shixiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19739","DOI":"10.1074\/jbc.M710098200","article-title":"Akt regulates the survival of vascular smooth muscle cells via inhibition of FoxO3a and GSK3","volume":"283","author":"Allard","year":"2008","journal-title":"J. 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