3-Nitropropionic acid exacerbates N-methyl-D-aspartate toxicity in striatal culture by multiple mechanisms

Neuroscience
J G GreeneJ T Greenamyre

Abstract

We examined the effects of 3-nitropropionic acid-induced succinate dehydrogenase inhibition on neuronal ATP content, N-methyl-D-aspartate-induced neuronal death, resting membrane potential, and N-methyl-D-aspartate-induced changes in cytosolic calcium concentration ([Ca2+]c) in cultured rat striatal neurons. Exposure of cultures to 3 mM 3-nitropropionic acid for 3 h did not cause overt toxicity, but reduced ATP content by 35%. Treatment with 3-nitropropionic, or removal of Mg2+ from the medium, enhanced subsequent N-methyl-D-aspartate toxicity, reducing the LC50 from 250 microM to 12 microM or 30 microM, respectively. Even after Mg2+ removal, enhancement of N-methyl-D-aspartate toxicity by 3-nitropropionic acid remained pronounced, with the LC50 further decreasing to 3 microM. The mean resting membrane potential of neurons treated with 3-nitropropionic acid was -37 mV, while that in control neurons was -61 mV. Treatment with 3-nitropropionic did not affect baseline [Ca2+]c as determined by fura-2 microfluorimetry. N-methyl-D-aspartate (30 microM) caused a rapid rise in [Ca2+]c, the initial magnitude of which was not affected by 3-nitropropionic acid. However, after a 1-h treatment, [Ca2+]c was dramatically higher in 3-nitroprop...Continue Reading

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Citations

Oct 9, 1999·Progress in Neurobiology·E BrouilletP Hantraye
Aug 30, 2002·The International Journal of Biochemistry & Cell Biology·David G Nicholls
Feb 13, 2001·British Journal of Pharmacology·D PubillA Camins
Feb 19, 2008·Archives of Medical Research·Ana María Estrada SánchezLourdes Massieu
Mar 21, 2007·Trends in Neurosciences·Paolo CalabresiMassimiliano Di Filippo
Aug 18, 2009·Journal of Neurochemistry·Ricardo LagoaCarlos Gutierrez-Merino
May 26, 2007·Journal of Neuroscience Research·Angélique D DucrayHans Rudolf Widmer
Jul 21, 2006·European Journal of Pharmacology·Massimiliano Di FilippoPaolo Calabresi
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Feb 5, 2015·BioMed Research International·Yie-Vern LeeYee Siew Choong
Jan 17, 2012·Brain Research Bulletin·Dirleise ColleMarcelo Farina
Aug 18, 2009·Biochimica Et Biophysica Acta·Maria DamianoEmmanuel Brouillet
Mar 31, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carine JacquardEmmanuel Brouillet
May 24, 2020·International Journal of Molecular Sciences·Carmen Lopez-SanchezCarlos Gutierrez-Merino
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Jun 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Heegyu KimKi-Bong Oh
Jan 14, 1999·Journal of Neurochemistry·M R Sánchez-Carbente, L Massieu
Jan 5, 2000·Physiological Reviews·D G Nicholls, S L Budd

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