title: High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1.
abstract: Cardiovascular disease is a serious complication in diabetic patients. To elucidate the precise mechanisms of atherosclerosis in diabetic patients, the effects of high glucose concentration (25 mM) on apoptosis regulation and bcl-2 family protein expression in human coronary artery smooth muscle cells (CASMC) were examined. Treatment with a high level of glucose (25 mM) caused a significant decrease in apoptosis in CASMC compared with the same cells treated with a physiologically normal glucose concentration (5.5 mM) (23.9 +/- 2.4% vs. 16.5 +/- 1.8%; P < 0.01). With respect to apoptosis regulation, treatment of CASMC with high glucose concentration markedly increased mRNA expressions of bcl-xL and bfl-1/A1 compared with cells treated with normal glucose. High glucose induced phosphorylation of phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase (ERK)1/2 along with bcl-xL and bfl-1/A1 upregulation. These results suggest that high glucose suppresses apoptosis via upregulation of bcl-xL and bfl-1/A1 levels through PI 3-K and ERK1/2 pathways in CASMC. High glucose-induced increase in the expression of antiapoptotic proteins may be important in the development of atherosclerosis in diabetic patients.
authors.affiliation: Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Sakuma
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Mie
authors.initials: M
authors.lastname: Okumura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kojima
authors.forename: Takako
authors.initials: T
authors.lastname: Maruyama
authors.forename: Keigo
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D015778:Minor Histocompatibility Antigens; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015854:Up-Regulation; D051020:bcl-X Protein
chemical_list: C096816:BCL2-related protein A1; C494811:BCL2L1 protein, human; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose