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T Yamauchi, S Kashii, Y Honda, A Akaike; Role Of Mitochondrial K(atp) Channel And Pkc On The Neuro-protection Against Glutamate Neurotoxicity . Invest. Ophthalmol. Vis. Sci. 2002;43(13):746.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously found the protective effect of bradykinin against glutamate neurotoxicity in cultured retinal neurons. We have also found that opening the ATP dependent potassium channel of mitochondria (Mit. K(ATP) channel) suppresses glutamate neurotoxicity. It is well known that Mit. K(ATP) channel is on the downstream of bradykinin in myocardia. The purpose of this study is to elucidate the mechanism of neuro-protection mediated by mitochondria. Methods: Primary cultures were obtained from the retina of fetal rats (gestation day 17-19). Cytosine arabinoside(10 µM) was added to the culture on the 6th day to eliminate non-neuronal cells. We used only those cultures maintained for 7-8 days in vitro. Glutamate neurotoxicity was assessed by 10-min exposure to 1mM glutamate followed by 1-hour incubation in glutamate free media, using trypan blue exclusion method. Bradikinin, diazoxide (the opener of Mit. K(ATP) channel), 5-HD (the blocker of Mit. K(ATP) channel) and chelerythrine (PKC inhibitor) were applied simultaneously with 1mM glutamate. Mitochondrial membrane potential was measured as the ratio of the 590nm/527nm fluorescence of JC-1. Results: Bradykinin suppressed the glutamate induced neurotoxicity, and this protective effect was inhibited by the simultaneous application of 5-HD. Diazoxide suppressed the glutamate induced neurotoxicity, and this protective effect was inhibited by the simultaneous application of chelerythrine. Bradykinin suppressed the glutamate induced mitochondrial depolization, and this suppression was inhibited by the simultaneous application of 5-HD. Conclusion: These results suggest that Mit. K(ATP) channel is on the downstream of bradykinin, and the PKC is on the downstream of Mit. K(ATP) channel.
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