{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:12:32Z","timestamp":1769548352973,"version":"3.49.0"},"reference-count":53,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"Macau Science and Technology Development Fund","award":["FDCT 0007\/2019\/AKP"],"award-info":[{"award-number":["FDCT 0007\/2019\/AKP"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830042"],"award-info":[{"award-number":["31830042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870212"],"award-info":[{"award-number":["81870212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670248"],"award-info":[{"award-number":["81670248"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:p> Endogenous hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) affects cholesterol homeostasis and liver X receptor \u03b1 (LXR\u03b1) expression. However, whether low-density lipoprotein (LDL) receptor (LDLR), a key player in cholesterol homeostasis, is regulated by exogenous H<jats:sub>2<\/jats:sub>S through LXR\u03b1 signaling has not been determined. We investigated the effects of sodium hydrosulfide (NaHS, H<jats:sub>2<\/jats:sub>S donor) on LDLR expression in the presence or absence of LXR agonists, T0901317 or GW3965 in HepG2 cells. We found that H<jats:sub>2<\/jats:sub>S strongly accumulated LDLR precursor in the presence of T0901317. Hence, LDLR transcription and the genes involved in LDLR precursor maturation and degradation were studied. T0901317 increased the LDLR mRNA level, whereas H<jats:sub>2<\/jats:sub>S did not affect LDLR transcription. H<jats:sub>2<\/jats:sub>S had no significant effect on the expression of LXR\u03b1 and inducible degrader of LDLR (IDOL). H<jats:sub>2<\/jats:sub>S and T0901317 altered mRNA levels of several enzymes for N- and O-glycosylation and endoplasmic reticulum (ER) chaperones assisting LDLR maturation, but did not affect their protein levels. H<jats:sub>2<\/jats:sub>S decreased proprotein convertase subtilisin\/kexin type 9 (PCSK9) protein levels and its mRNA level elevated by T0901317. T0901317 with PCSK9 siRNA also accumulated LDLR precursor as did T0901317 with H<jats:sub>2<\/jats:sub>S. High glucose increased PCSK9 protein levels and attenuated LDLR precursor accumulation induced by T0901317 with H<jats:sub>2<\/jats:sub>S. Taken together, H<jats:sub>2<\/jats:sub>S accumulates LDLR precursor by downregulating PCSK9 expression but not through the LXR\u03b1-IDOL pathway, LDLR transcriptional activation, or dysfunction of glycosylation enzymes and ER chaperones. These results also indicate that PCSK9 plays an important role in LDLR maturation in addition to its well-known effect on the degradation of LDLR mature form. <\/jats:p>","DOI":"10.1152\/ajpcell.00244.2019","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T01:18:16Z","timestamp":1600305496000},"page":"C1082-C1096","source":"Crossref","is-referenced-by-count":7,"title":["Hydrogen sulfide accumulates LDL receptor precursor via downregulating PCSK9 in HepG2 cells"],"prefix":"10.1152","volume":"319","author":[{"given":"Yong","family":"Huang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Bioactive Small Molecules and Shanghai Key Laboratory of Clinical Geriatric Medicine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Ning","sequence":"additional","affiliation":[{"name":"Shanghai Key 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