Both
Melatonin and a Putative Nuclear Melatonin Receptor Agonist
CGP 52608 Stimulate Glutathione Peroxidase and Glutathione Reductase
Activities in Mouse Brain In Vivo by Marta I. Pablos, Juan M. Guerrero, Genaro G. Ortiz, Maria
T. Agapito and Russel J. Reiter
Department of Cellular and Structural Biology, University of
Texas, The Health Science Center at San Antonio. San Antonio,
TX78284-7762, U.S.A.
Abstract
Melatonin is both a direct and indirect antioxidant. Thus, it
scavenges a variety of free radicals and it stimulates the antioxidative
enzyme glutathione peroxidase. Melatonin has been shown to enter
the brain and to accumulate in the nucleus of cells. A high-affinity
nuclear binding site/receptor for melatonin has been tentatively
identified. Using an agonist of the putative nuclear receptor,
we show here that the agonist duplicates the stimulatory effect
of melatonin on cerebral and cerebellar glutathione peroxidase
activity in vivo. We also report that both melatonin
and the agonist stimulate glutathione reductase activity. The
increases in both enzyme activities are time-dependent, but
the stimulation in glutathione reductase activity is delayed
compared to that of glutathione peroxidase. The results indicate
that melatonin's ability to protect the brain from oxidative
damage may be in part be a consequence of a receptor-mediated
stimulation of neural antioxidative enzymes.