Mechanism of resistance to NO-induced neurotoxicity in cultured rat dopaminergic neurons

Journal of Neuroscience Research
H SawadaJ Kimura

Abstract

We previously reported that mesencephalic dopaminergic neurons are resistant to cytotoxicity induced by nitric oxide (NO). This study investigated the intracellular mechanism that protects dopaminergic neurons against NO toxicity in rat mesencephalic cultures. Peroxynitrite anion, an active metabolite of NO, caused significant cytotoxic effects against dopaminergic and nondopaminergic neurons, but NO caused cytotoxic effects restricted to nondopaminergic neurons. In addition, we studied the effects of ascorbate, an anti-oxidant, on NO-induced neurotoxicity against dopaminergic neurons and found that coadministration of ascorbate failed to affect resistance against NO-induced neurotoxicity. These findings suggest that the protecting mechanism from NO neurotoxicity in dopaminergic neurons is based on inhibition of conversion of NO to peroxynitrite anion, is independent of the NO redox state, and is possibly due to suppression of superoxide anion production. Furthermore, we investigated NO-induced neurotoxicity with or without pretreatment with sublethal doses of methylphenylpyridium ion (MPP+). Following pretreatment with 1 microM MPP+, which did not show significant cytotoxic effects against dopaminergic neurons, NO demonstrated...Continue Reading

References

Jan 1, 1992·Neuron·D S Bredt, S H Snyder
Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·V L DawsonS H Snyder
Feb 1, 1991·Trends in Neurosciences·J Garthwaite
Apr 1, 1991·Trends in Pharmacological Sciences·S H Snyder, D S Bredt
Mar 1, 1990·Journal of Neurochemistry·A H SchapiraC D Marsden
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J S BeckmanB A Freeman
Dec 1, 1989·Annals of Neurology·W D ParkerJ K Parks
Nov 17, 1994·Annals of the New York Academy of Sciences·S A LiptonJ S Stamler
Jun 22, 1993·The Journal of Comparative Neurology·M D Johnson, P M Ma
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·D A WinkJ B Mitchell

❮ Previous
Next ❯

Citations

Dec 25, 2013·European Journal of Pharmacology·Sandra OsterGabriele Gille
Jul 26, 2003·Antioxidants & Redox Signaling·Manuchair Ebadi, Sushil K Sharma
Jun 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H SawadaS Shimohama
Jan 4, 2001·Japanese Journal of Pharmacology·Y KitamuraT Taniguchi
Jul 12, 2001·The Journal of Biological Chemistry·K NakamuraU J Kang
Dec 10, 2003·Neuroreport·Noriko SakkaAkinori Akaike
Sep 8, 2017·Advanced Healthcare Materials·Tatsuya OsakiRoger D Kamm
Feb 28, 2002·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Akinori AkaikeToshiaki Kume
Dec 8, 1998·Journal of Neuroscience Research·H SawadaS Shimohama
Aug 21, 2003·Trends in Molecular Medicine·Shun ShimohamaTakashi Taniguchi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.