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• W2015590649 startingPage "3378" @default.
• W2015590649 abstract "Activation of the nuclear enzyme poly(ADP-ribose)-1 leads to the death of neurons and other types of cells by a mechanism involving NAD(+) depletion and mitochondrial permeability transition. It has been proposed that the mitochondrial permeability transition (MPT) is required for NAD(+) to be released from mitochondria and subsequently consumed by PARP-1. In the present study we used the MPT inhibitor cyclosporine-A (CsA) to preserve mitochondrial NAD(+) pools during PARP-1 activation and thereby provide an estimate of mitochondrial NAD(+) pool size in different cell types. Rat cardiac myocytes, mouse cardiac myocytes, mouse cortical neurons, and mouse cortical astrocytes were incubated with the genotoxin N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in order to activate PARP-1. In all four cell types MNNG caused a reduction in total NAD(+) content that was blocked by the PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone. Inhibition of the mitochondrial permeability transition with cyclosporine-A (CsA) prevented PARP-1-induced NAD(+) depletion to a varying degree in the four cell types tested. CsA preserved 83.5% +/- 5.2% of total cellular NAD(+) in rat cardiac myocytes, 85.7% +/- 8.9% in mouse cardiac myocytes, 55.9% +/- 12.9% in mouse neurons, and 22.4% +/- 7.3% in mouse astrocytes. CsA preserved nearly 100% of NAD(+) content in mitochondria isolated from these cells. These results confirm that it is the cytosolic NAD(+) pool that is consumed by PARP-1 and that the mitochondrial NAD(+) pool is consumed only after MPT permits mitochondrial NAD(+) to exit into the cytosol. These results also suggest large differences in the mitochondrial and cytosolic compartmentalization of NAD(+) in these cell types." @default.
• W2015590649 created "2016-06-24" @default.
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• W2015590649 date "2007-09-12" @default.
• W2015590649 modified "2023-10-10" @default.
• W2015590649 title "Differences among cell types in NAD+ compartmentalization: A comparison of neurons, astrocytes, and cardiac myocytes" @default.
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• W2015590649 doi "https://doi.org/10.1002/jnr.21479" @default.
• W2015590649 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17853438" @default.
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