TY - JOUR
T1 - Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase inhibitor)-induced fragmentation and condensation of DNA in NG108-15 cells
AU - Nakazawa, Minako
AU - Uehara, Takashi
AU - Nomura, Yasuyuki
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1997/6
Y1 - 1997/6
N2 - We examined nitric oxide (NO)-induced cell death in NG108-15 cells using NO donors. Both sodium nitroprusside (SNP) and S-nitroso-N- acetylpenicillamine caused lactate dehydrogenase (LDH) leakage from NG108-15 cells. NO is known to increase the amount of radioisotopic labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the presence of [32P]NAD and to inhibit the enzyme activity. To clarify the relationship between the NO-induced inhibition of GAPDH activity and cell death, we studied the effect of koningic acid (KA), a potent selective inhibitor of GAPDH. Both SNP and KA elicited LDH leakage, chromosomal condensation, and fragmentation of nuclei in NG108-15 cells. Gel electrophoretic analysis of cellular DNA extracted from SNP- and KA-treated cells revealed the internucleosomal DNA fragmentation typical of apoptosis in these cultures. The results suggested that in NG108-15 cells, (a) the inhibition of GAPDH activity results in apoptosis and (b) SNP-induced cell death is partly due to the NO-induced inhibition of GAPDH, perhaps by stimulating the binding of NAD to GAPDH.
AB - We examined nitric oxide (NO)-induced cell death in NG108-15 cells using NO donors. Both sodium nitroprusside (SNP) and S-nitroso-N- acetylpenicillamine caused lactate dehydrogenase (LDH) leakage from NG108-15 cells. NO is known to increase the amount of radioisotopic labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the presence of [32P]NAD and to inhibit the enzyme activity. To clarify the relationship between the NO-induced inhibition of GAPDH activity and cell death, we studied the effect of koningic acid (KA), a potent selective inhibitor of GAPDH. Both SNP and KA elicited LDH leakage, chromosomal condensation, and fragmentation of nuclei in NG108-15 cells. Gel electrophoretic analysis of cellular DNA extracted from SNP- and KA-treated cells revealed the internucleosomal DNA fragmentation typical of apoptosis in these cultures. The results suggested that in NG108-15 cells, (a) the inhibition of GAPDH activity results in apoptosis and (b) SNP-induced cell death is partly due to the NO-induced inhibition of GAPDH, perhaps by stimulating the binding of NAD to GAPDH.
KW - Apoptosis
KW - Glyceraldehyde-3-phosphate dehydrogenase
KW - Nitric oxide
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U2 - 10.1046/j.1471-4159.1997.68062493.x
DO - 10.1046/j.1471-4159.1997.68062493.x
M3 - Article
C2 - 9166744
AN - SCOPUS:0030930536
VL - 68
SP - 2493
EP - 2499
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -