title: Grape seed procyanidin B2 ameliorates mitochondrial dysfunction and inhibits apoptosis via the AMP-activated protein kinase-silent mating type information regulation 2 homologue 1-PPARγ co-activator-1α axis in rat mesangial cells under high-dose glucosamine.
abstract: Grape seed procyanidin B2 (GSPB2), an antioxidative and anti-inflammatory polyphenol in grape seed, has been found to have protective effects on diabetic nephropathy. Based on its favourable biological activities, in the present study, we aimed to investigate whether GSPB2 could inhibit apoptosis in rat mesangial cells treated with glucosamine (GlcN) under high-dose conditions. The results showed that the administration of GSPB2 (10 μg/ml) significantly increased the viability of mesangial cells treated with GlcN at a dose of 15 mM. We found that GSPB2 inhibited apoptosis in mesangial cells using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphates (dUTP) nick-end labelling staining and flow cytometry technique (P< 0·05 for both). GSPB2 treatment also suppressed oxidative stress by elevating the activity of glutathione peroxidase (P< 0·05) and superoxide dismutase (P< 0·01), as well as prevented cellular damage. GSPB2 enhanced the mRNA expression of nuclear respiratory factor 1, mitochondrial transcription factor A and mitochondrial DNA copy number in mesangial cells as determined by real-time PCR (P< 0·05 for each). Finally, GSPB2 treatment activated the protein expression of PPARγ co-activator-1α (PGC-1α), silent mating type information regulation 2 homologue 1 (SIRT1) and AMP-activated protein kinase (AMPK) in mesangial cells. These findings suggest that GSPB2 markedly ameliorates mitochondrial dysfunction and inhibits apoptosis in rat mesangial cells treated with high-dose GlcN. This protective effect could be, at least in part, due to the activation of the AMPK-SIRT1-PGC-1α axis.
authors.affiliation: Department of Nutrition and Food Hygiene,School of Public Health, Peking University,Beijing100191,People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Nutrition and Food Hygiene,School of Public Health, Peking University,Beijing100191,People's Republic of China.
authors.forename: Xiaxia
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Nutrition and Food Hygiene,School of Public Health, Peking University,Beijing100191,People's Republic of China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene,School of Public Health, Peking University,Beijing100191,People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D003928:Diabetic Nephropathies / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000008:administration & dosage / Q000009:adverse effects*; D056604:Grape Seed Extract / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D012639:Seeds / Q000737:chemistry; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D027843:Vitis / Q000737:chemistry
chemical_list: D044946:Biflavonoids; D056604:Grape Seed Extract; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D044945:Proanthocyanidins; D014157:Transcription Factors; C479580:procyanidin B2; D002392:Catechin; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005944:Glucosamine
keywords: Apoptosis; Diabetic nephropathy; Grape seed procyanidin B2; Mesangial cells; Mitochondrial dysfunction