An endogenous metabolite of dopamine, 3,4-dihydroxyphenylethanol, acts as a unique cytoprotective agent against oxidative stress-induced injury.
A natural compound contained in olive oil, 3,4-dihydroxyphenylethanol (DOPE), is also known as an endogenous metabolite of dopamine. The role of DOPE in oxidative stress-induced cell damage was investigated using differentiated PC12 cells. Superoxide (O(2)(-)) and H(2)O(2) induced a dose-dependent leakage of lactate dehydrogenase (LDH) and decreased cell viability denoted by MTT assay. While O(2)(-) -induced cell damage was not affected by DOPE, pretreatment of the cells with DOPE dose-dependently prevented the leakage of LDH induced by H(2)O(2). In these cells, augmented activity of catalase was demonstrated, while the levels of glutathione and glutathione peroxidase activity remained unchanged. The effect of DOPE was abolished when an inhibitor of catalase 3-amino-l, 2,4-triazole, was included in the medium. DOPE also protected against cell damage induced by H(2)O(2), and Fe(2+). In the hydroxyl radical ((.-)OH) assay using p-nitroso-N, N-dimethylaniline (PNDA), oxidation of PNDA by (.-)OH generated by the Fenton reaction was significantly attenuated in the presence of DOPE. By an electron spin resonance spin trapping study that represents the direct activity of DOPE to scavenge (.-)OH, however, limited scavenging activity was demonstrated for DOPE. Taken together, DOPE may act as a unique cytoprotective compound in nerve tissue subjected to oxidative stress.
Department of Pharmacology, Kyoto, Prefectural University of Medicine, Kyoto, Japan.
Tsuneichi
T
Hashimoto
Masakazu
M
Ibi
Kuniharu
K
Matsuno
Shingo
S
Nakashima
Toru
T
Tanigawa
Toshikazu
T
Yoshikawa
Chihiro
C
Yabe-Nishimura
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism*; D051381:Rats; D013481:Superoxides / Q000633:toxicity
D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; C005975:3,4-dihydroxyphenylethanol; D013481:Superoxides; C013160:4-nitroso-N,N-diethylaniline; D006861:Hydrogen Peroxide; D007501:Iron; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D010626:Phenylethyl Alcohol; D004298:Dopamine; D000640:Amitrole