Cellular response to the redox active lipid peroxidation products: induction of glutathione S-transferase P by 4-hydroxy-2-nonenal.
Membrane lipid peroxidation is known to produce various aldehydic compounds which cause a wide range of biological effects including heart disease, aging, and cancer. To investigate the effect of lipid peroxidation products on the expression of glutathione S-transferases (GSTs), which catalyze the conjugation of reactive chemicals with glutathione and play an important role in protecting cells, normal rat liver epithelial cells (RL34) were exposed to a variety of aldehydic compounds. We found that the GST activity in RL34 cells was induced by alpha,beta-unsaturated aldehydes, such as acrolein (1.3-fold), crotonaldehyde (1.3-fold), 4-hydroxy-2-hexenal (HHE) (1.4-fold), and 4-hydroxy-2-nonenal (HNE) (1.7-fold). The induction of GST activity by HNE was time-dependent, reaching a plateau after 16 h. The immunoblot analysis using the polyclonal antibodies against GST isozymes demonstrated that GST-P (pi-class), a well-known tumor marker, was significantly induced 16 h after the HNE treatment. Also, immunostaining for the presence of GST-P confirmed the enhanced expression of GST-P in the cytoplasm of the cells. Northern blot analysis revealed that the HNE treatment of RL34 cells for 1 h enhanced the expression of GST-P mRNA, which returned to the control level after 16 h. These data suggest that the induction of GST-P by HNE may represent an important cellular defense mechanism against oxidative injury.
Fukuda
A
A
Laboratory of Food and Biodynamics, Nagoya University School of Agricultural Sciences, Japan.
Nakamura
Y
Y
Ohigashi
H
H
Osawa
T
T
Uchida
K
K
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects*; D004848:Epithelium / Q000201:enzymology; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007124:Immunoenzyme Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D000447:Aldehydes; D008054:Lipid Peroxides; D012333:RNA, Messenger; D005982:Glutathione Transferase; C027576:4-hydroxy-2-nonenal