Protective effect of L-carnosine against 12-O-tetradecanoylphorbol-13-acetate- or hydrogen peroxide-induced apoptosis on v-myc transformed rat liver epithelial cells.
Apoptotic processes have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease etc. beta-Alanyl-L-histidine (L-carnosine), occurring abundantly in skeletal muscles has been suggested to possess antioxidative activity. We investigated whether L-carnosine prevents 12-O-tetradecanoylphorbol-13-acetate (TPA)- or hydrogen peroxide (H2O2)-induced apoptosis involving mitochondria in the v-myc transformed rat liver epithelial cells (WB-myc cells). L-Carnosine prevented both TPA- and H2O2-induced DNA fragmentation, the loss of mitochondrial membrane potentials and blocked the release of cytochrome c into cytosol. Subsequently, the cleavages of poly (ADP-ribose) polymerase were significantly reduced in L-carnosine-treated cells. However, western blotting analysis revealed that p53 protein level did not change for 12h after TPA- and H2O2-treatment. Therefore, these results suggested that L-carnosine, an antioxidant, protected both H2O2- and TPA-induced apoptosis through mitochondrial pathways.
Kang
Kyung Sun
KS
Department of Veterinary Public Health, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, 103 Seodun-dong, Kwonsun-ku, Suwon 441-744, South Korea.
Yun
Jun Won
JW
Lee
Yong Soon
YS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D015153:Blotting, Western; D002336:Carnosine / Q000494:pharmacology*; D002461:Cell Line, Transformed / Q000187:drug effects; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D016259:Genes, myc / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D020112:Rhodamine 123; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D003574:Cytochrome c Group; D016159:Tumor Suppressor Protein p53; D020112:Rhodamine 123; D002336:Carnosine; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D006690:Bisbenzimidazole; D013755:Tetradecanoylphorbol Acetate