Endomorphins, endogenous opioid peptides, provide antioxidant defense in the brain against free radical-induced damage.
Oxidative stress has been considered to be a major cause of cellular injuries in a variety of chronic health problems, such as carcinogenesis and neurodegenerative disorders. The brain appears to be more susceptible to oxidative damage than other organs. Therefore, the existence of antioxidants may be essential in brain protective systems. The antioxidative and free radical scavenging effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, have been investigated in vitro. The oxidative damage was initiated by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrocholoride) (AAPH) and hydrogen peroxide (H2O2). The linoleic acid peroxidation, DNA and protein damage were monitored by formation of hydroperoxides, by plasmid pBR 322 DNA nicking assay and single-cell alkaline electrophoresis, and by SDS-polyacrylamide gel electrophoresis. Endomorphins can inhibit lipid peroxidation, DNA strand breakage, and protein fragmentation induced by free radical. Endomorphins also reacted with galvinoxyl radicals in homogeneous solution, and the pseudo-first-order rate constants were determined spectrophotometrically by following the disappearance of galvinoxyl radicals. In all assay systems, EM1 was more potent than EM2 and GSH, a major intracellular water-soluble antioxidant. We propose that endomorphins are one of the protective systems against free radical-induced damage in the brain.
Lin
Xin
X
Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Tianshui Road 298 #, Lanzhou, Gansu 730000, China.
Yang
Ding-Jian
DJ
Cai
Wen-Qing
WQ
Zhao
Qian-Yu
QY
Gao
Yan-Feng
YF
Chen
Qiang
Q
Wang
Rui
R
D000578:Amidines / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008823:Micelles; D009153:Mutagens / Q000633:toxicity; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000578:Amidines; D000975:Antioxidants; D005609:Free Radicals; D008823:Micelles; D009153:Mutagens; D009842:Oligopeptides; C105293:endomorphin 1; C105294:endomorphin 2; C046728:2,2'-azobis(2-amidinopropane)