title: Critical role of prohibitin in endothelial cell apoptosis caused by glycated low-density lipoproteins and protective effects of grape seed procyanidin B2.
abstract: Elevated level of glycated low-density lipoproteins (glyLDL) is believed to contribute to endothelial dysfunction, which is involved in the pathogenesis and acceleration of diabetic vascular diseases. Grape seed procyanidin B2 (GSPB2) has been reported to possess protective effects against endothelial dysfunction. However, the underlying mechanism remains unclear. Prohibitin (PHB) is a multifunctional protein implicated in cellular survival and apoptosis. In this study, we showed that glyLDL treatment decreased protein level of PHB, reduced viability, and increased apoptosis in human umbilical vein endothelial cells (HUVEC). PHB overexpression or GSPB2 significantly attenuated apoptosis induced by glyLDL. Moreover, PHB siRNA increased HUVEC apoptosis, along with defective mitochondria and increased levels of cytosol cytochrome c concentration, caspase-3 activity, Bax/Bcl-2 ratio, and phosphorylated Akt, whereas PHB overexpression or GSPB2 restored these changes. Our study identified PHB as an important player responsible for HUVEC apoptosis induced by glyLDL. GSPB2 protected against HUVEC apoptosis at least in part through upregulating PHB. Targeting PHB could be significant in fighting against diabetic vascular complications.
authors.affiliation: *Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China; †Institute of Basic Science, Medical Science Academy of Shandong, Jinan, China; and ‡Division of Cardiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Yin
authors.forename: Baoying
authors.initials: B
authors.lastname: Li
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Junfu
authors.initials: J
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Ruihai
authors.initials: R
authors.lastname: Zhou
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.forename: Haiqing
authors.initials: H
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D002392:Catechin / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D056604:Grape Seed Extract / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008928:Mitochondria / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D000091402:Prohibitins; D034741:RNA, Small Interfering / Q000008:administration & dosage; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D044946:Biflavonoids; D056604:Grape Seed Extract; D008077:Lipoproteins, LDL; C000717328:PHB protein, human; D044945:Proanthocyanidins; D000091402:Prohibitins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C479580:procyanidin B2; D002392:Catechin