Grape seed procyanidin B2 inhibits advanced glycation end product-induced endothelial cell apoptosis through regulating GSK3β phosphorylation.
To investigate the effects of GSPB2 (grape seed procyanidin B2) on the apoptosis of HUVECs (human umbilical endothelial cells) induced by AGEs (advanced glycation end products), HUVECs were treated with AGEs (200 μg/ml) in the presence or absence of GSPB2 (2.5, 5.0 and 10.0 μmol/l). Our findings showed that (i) AGEs induced HUVEC apoptosis and up-regulated the expression of caspase-3 activation and lactadherin and reduced the phosphorylation of GSK3β (glycogen synthase kinase 3β) at baseline. (ii) Treatment of HUVEC with GSPB2 significantly inhibited the cell apoptosis and the expression of caspase-3 activation and lactadherin induced by AGEs. Moreover, GSPB2 inhibited intracellular reactive oxygen species in a dose-dependent manner in AGEs-treated cells as determined by flow cytometry. (iii) GSPB2 increased the phosphorylation of GSK3β of HUVEC in response to AGEs. These findings suggest that the signalling pathway involving phosphorylation of GSK3β and lactadherin might play a key role in the endothelial apoptosis. GSPB2 therapy could become an effective approach to battling AGEs-induced endothelial apoptosis.
Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, QiLu Hospital of Shandong University, Jinan, Shandong Province, Peoples Republic of China.
Bao-ying
BY
Li
Xiao-li
XL
Li
Hai-qing
HQ
Gao
Jian-hua
JH
Zhang
Qian
Q
Cai
Mei
M
Cheng
Mei
M
Lu
D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors; D002392:Catechin / Q000494:pharmacology / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D056604:Grape Seed Extract / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008894:Milk Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D044945:Proanthocyanidins / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D027843:Vitis / Q000737:chemistry
D000954:Antigens, Surface; D044946:Biflavonoids; D061945:Caspase Inhibitors; D017127:Glycation End Products, Advanced; D056604:Grape Seed Extract; C098942:MFGE8 protein, human; D008894:Milk Proteins; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; C479580:procyanidin B2; D002392:Catechin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3