title: (-)-Epigallocatechin gallate suppresses proliferation of vascular smooth muscle cells induced by high glucose by inhibition of PKC and ERK1/2 signalings.
abstract: Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of diabetes-related vascular complications. (-)-Epigallocatechin gallate (EGCG), the major catechin derived from green tea, is able to exert antidiabetes effects in animal models. However, it is not known whether or not EGCG inhibits VSMC proliferation induced by high glucose. This study tested the hypothesis that EGCG might have an inhibitory effect on VSMC proliferation induced by high glucose. VSMC proliferation was determined by [(3)H]-thymidine incorporation and uptake of 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT). Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was determined by immunoblotting, and ERK 1/2 activity was detected by measuring the ability to phosphorylate its substrate Elk-1. Glucose increased VSMC proliferation in a concentration-dependent manner, which was reduced in the presence of EGCG. VSMC proliferation mediated by high glucose (30 mM) was involved in protein kinase C (PKC) and ERK1/2 signalings, because its effect was blocked by PKC inhibitor (PKC inhibitor 19-31) and ERK1/2 inhibitor (PD98059). Pretreatment of VSMCs with EGCG significantly inhibited the stimulatory effect of high glucose on PKC and ERK1/2 activation, followed by attenuation of its downstream transcription factor Elk-1 phosphorylation. Taken together, these results suggest that EGCG could suppress VSMC proliferation induced by high glucose by inhibition of PKC and ERK1/2 signalings in VSMCs, which indicates that EGCG might be a possible medicine to reduce vascular complications in diabetes.
authors.affiliation: Department of Nutrition, Daping Hospital, The Third Military Medical University, Chongqing, 400042 People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Hailan
authors.initials: H
authors.lastname: Sun
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Changqing
authors.initials: C
authors.lastname: Yu
authors.forename: Baoquan
authors.initials: B
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D002392:Catechin; C045651:epigallocatechin gallate; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose