meso-Dihydroguaiaretic acid attenuates the neurotoxic effect of staurosporine in primary rat cortical cultures.
The effect of meso-dihydroguaiaretic acid (MDGA) on the staurosporine-induced neuronal apoptosis and its potential mechanism were investigated using primary cultures of rat cortical cells as an assay system. Treatment of MDGA at the concentrations of 0.1, 1.0 and 10 microM significantly protected neuronal cells against Staurosporine-induced apoptosis. The neuroprotective activity of MDGA was the most potent at the concentration of 1.0 microM and was not increased at higher concentration. MDGA reduced apoptotic characteristics induced by STS; MDGA reduced the condensed nuclei in staurosporine-injured rat cortical cells. MDGA diminished the calcium influx that accompanies the staurosporine-induced apoptosis, and inhibited the subsequent overproduction of reactive oxygen species and peroxide to the level of control cells. It also preserved cellular activity of superoxide dismutase, an antioxidative enzyme reduced by staurosporine insult. In addition, MDGA significantly inhibited caspase-3/7 activation and cytochrome c release. Taken together, these results suggested that MDGA protected neuronal cells against staurosporine-induced apoptosis through the inhibition of Ca(2+) influx, cellular oxidation, cytochrome c release and caspase-3/7 activation.
Ma
Choong Je
CJ
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, San56-1, Sillim-Dong, Gwanak-Gu, Seoul 151-742, South Korea.
Lee
Mi Kyeong
MK
Kim
Young Choong
YC
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D045304:Cytochromes c / Q000378:metabolism; D003619:Dansyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005688:Galactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000633:toxicity*
D003619:Dansyl Compounds; D017705:Lignans; D009498:Neurotoxins; D010545:Peroxides; C079425:methyl-N-dansylgalactosaminide; C015816:dihydroguaiaretic acid; D006139:Guaiacol; D005688:Galactosamine; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine; D002118:Calcium