title: Protective effect of D-alpha-tocopherol on the function of human mesangial cells exposed to high glucose concentrations.
abstract: Altered functions of mesangial cells (MCs) induced by high glucose levels are thought to play an important role in the pathogenesis of diabetic nephropathy. We investigate whether D-alpha-tocopherol (Toc), an antioxidant, can prevent malfunction of cultured human MCs induced by high-glucose media. Incubating MCs with 33 mmol/L glucose caused increased lipid peroxide (LPO) levels, disturbed cell replication, enhanced cytotoxicity, enhanced activity of the diacylglycerol (DAG)-protein kinase C (PKC) pathway, and overproduction of fibronectin and eicosanoids (6-keto prostaglandin F1 alpha [PGF1 alpha] and thromboxane B2 [TXB2]). The amount of LPO in MCs grown in 5 mmol/L glucose was reduced by the addition of Toc in a dose-dependent manner. Since the maximum effect of Toc on decreasing LPO was achieved at a concentration of 100 mumol/L, this dose was selected for the following experiments. Addition of Toc prevented increased LPO levels and [51Cr]-release from MCs induced by high-glucose media without affecting cell number. Toc decreased the total DAG level and PKC activity in membrane fractions in MCs cultured at both 5 and 33 mmol/L glucose. Furthermore, glucose-induced overproduction of fibronectin and eicosanoids from MCs was completely abolished by Toc. These results strongly suggest that Toc ameliorates glucose-induced malfunctions of MCs in vitro.
authors.affiliation: Second Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tada
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: S
authors.initials: S
authors.lastname: Isogai
mesh_terms: D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D002860:Chromium Radioisotopes; D004075:Diglycerides / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D002860:Chromium Radioisotopes; D004075:Diglycerides; D015777:Eicosanoids; D005353:Fibronectins; D008054:Lipid Peroxides; D002857:Chromium; D014810:Vitamin E; D011493:Protein Kinase C; D005947:Glucose