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Target Concepts:
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Query: EC:6.5.1.2 (
DNA ligase
)
2,749
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Both H2O2 (IC50 = 70 microM) and HOCl (IC50 = 8.5 microM) inhibited mitogen-induced MNL proliferation in a dose-dependent manner. This was found to be due to a depletion of intracellular ATP by at least two distinct mechanisms. HOCl and high concentrations (greater than 100 microM) of H2O2 inhibit ATP generation via sulfhydryl group oxidation on the active site of the
glyceraldehyde-3-phosphate dehydrogenase
(G3PDH) enzyme of the glycolytic pathway. On the other hand, low H2O2 concentrations cause ATP depletion by an activation of the
DNA repair enzyme
, poly(ADP-ribose)polymerase (pADPRP), leading to consumption of NAD+, an essential cofactor for G3PDH. The anti-oxidants ascorbate and cysteine protected MNL against the anti-proliferative effects of HOCl. Similar results were achieved with the HOCl-mediated inhibition of ATP production and G3PDH activity. However, ascorbate was unable to protect against H2O2-mediated inhibition of MNL functions, while cysteine protected against the inhibitory effects on ATP production and G3PDH activity, induced by this oxidant.
...
PMID:Biochemical mechanisms of hydrogen peroxide- and hypochlorous acid-mediated inhibition of human mononuclear leukocyte functions in vitro: protection and reversal by anti-oxidants. 132 47
Recent studies indicating a role of
glyceraldehyde-3-phosphate dehydrogenase
(
GAPDH
) in apoptosis or oxidative stress has been reported. Using confocal laser-scanning microscopy, we have investigated the cellular distribution of
GAPDH
in central nervous system (CNS)-derived cells (neuroblastoma mNB41A3), in non-CNS derived cells (R6 fibroblast) and in an apoptosis-resistant Bcl2 overexpressing cell line (R6-Bcl2). Induction of apoptosis by staurosporine or MG132 and oxidative stress by H(2)O(2) or FeCN enhanced the nuclear translocation of endogenous
GAPDH
in all cell types, as detected by immunocytochemistry. In apoptotic cells,
GAPDH
expression is three times higher than in non-apoptotic cells. Consistent with a role for
GAPDH
in apoptosis, overexpression of a
GAPDH
-green fluorescent protein (GAPDH-GFP) hybrid increased nuclear import of
GAPDH
-GFP into transfected cells and the number of apoptotic cells, and made them more sensitive to agents that induce apoptosis. Bcl2 overexpression prevents nuclear translocation of
GAPDH
and apoptosis in untransfected cells, but not in transfected cells that overexpress
GAPDH
-GFP. Our observations indicate that nuclear translocation of
GAPDH
may play a role in apoptosis and oxidative stress, probably related to the activity of
GAPDH
as a
DNA repair enzyme
or as a nuclear carrier for pro-apoptotic molecules.
...
PMID:Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. 1130 96
Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMCs that involves interaction of nuclear
glyceraldehyde-3-phosphate dehydrogenase
(
GAPDH
) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized
DNA repair enzyme
.
GAPDH
down-regulation potentiated H
2
O
2
-induced DNA damage and SMC apoptosis. Conversely,
GAPDH
overexpression decreased DNA damage and protected SMCs against apoptosis. Ape1 down-regulation reversed the resistance of
GAPDH
-overexpressing cells to DNA damage and apoptosis, which indicated that Ape1 is indispensable for
GAPDH
-dependent protective effects.
GAPDH
bound Ape1 in the SMC nucleus, and blocking (or oxidation) of
GAPDH
active site cysteines suppressed
GAPDH
/Ape1 interaction and potentiated apoptosis.
GAPDH
up-regulated Ape1
via
a transcription factor homeobox protein Hox-A5-dependent mechanism.
GAPDH
levels were reduced in atherosclerotic plaque SMCs, and this effect correlated with oxidative stress and SMC apoptosis. Thus, we demonstrated that nuclear
GAPDH
/Ape1 interaction preserved Ape1 activity, reduced DNA damage, and prevented SMC apoptosis. Suppression of SMC apoptosis by maintenance of nuclear
GAPDH
/Ape1 interactions may be a novel therapy to increase atherosclerotic plaque stability.-Hou, X., Snarski, P., Higashi, Y., Yoshida, T., Jurkevich, A., Delafontaine, P., Sukhanov, S. Nuclear complex of
glyceraldehyde-3-phosphate dehydrogenase
and
DNA repair enzyme
apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death.
...
PMID:Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death. 2840 43
