Protection of cells from oxidative stress by microsomal glutathione transferase 1.
Rat liver microsomal glutathione transferase 1 (MGST1) is a membrane-bound enzyme that displays both glutathione transferase and glutathione peroxidase activities. We hypothesized that physiologically relevant levels of MGST1 is able to protect cells from oxidative damage by lowering intracellular hydroperoxide levels. Such a role of MGST1 was studied in human MCF7 cell line transfected with rat liver mgst1 (sense cell) and with antisense mgst1 (antisense cell). Cytotoxicities of two hydroperoxides (cumene hydroperoxide (CuOOH) and hydrogen peroxide) were determined in both cell types using short-term and long-term cytotoxicity assays. MGST1 significantly protected against CuOOH and against hydrogen peroxide (although less pronounced and only in short-term tests). These results demonstrate that MGST1 can protect cells from both lipophilic and hydrophilic hydroperoxides, of which only the former is a substrate. After CuOOH exposure MGST1 significantly lowered intracellular ROS as determined by FACS analysis.
Siritantikorn
Atchasai
A
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Johansson
Katarina
K
Ahlen
Karin
K
Rinaldi
Rosanna
R
Suthiphongchai
Tuangporn
T
Wilairat
Prapon
P
Morgenstern
Ralf
R
D002460:Cell Line; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008862:Microsomes, Liver / Q000201:enzymology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D005982:Glutathione Transferase