title: Buthionine sulfoximine promotes methylglyoxal-induced apoptotic cell death and oxidative stress in endothelial cells.
abstract: Methylglyoxal (MG), a reactive dicarbonyl produced during glucose metabolism, is found at high levels in the blood of diabetic patients. MG induces oxidative stress and apoptosis. There is evidence that MG causes glutathione (GSH) depletion. However, it remains unknown whether GSH plays a protective role against the cytotoxic effect of MG. We examined the effect of DL-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the viability of bovine aortic endothelial cells (BAECs) exposed to MG. BAECs pretreated with BSO showed reduced ability to survive MG exposure. Flow cytometric analyses with annexin V and propidium iodide double staining revealed that BAECs exposed to MG after BSO pretreatment displayed features characteristic of apoptosis. Caspase-3 activation induced by MG was increased by BSO. Moreover, measurement of protein carbonyl levels showed that BSO promoted MG-induced oxidative stress. Taken together, these findings suggest that the depletion of GSH via BSO pretreatment promoted MG-induced apoptotic cell death and oxidative stress in BAECs.
authors.affiliation: School of Pharmacy, Hokkaido Pharmaceutical University, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Takahashi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tatsunami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oba
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tampo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D011765:Pyruvaldehyde / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D011765:Pyruvaldehyde; D053148:Caspase 3; D005978:Glutathione