TY - JOUR
T1 - Nitric oxide mediated induction of cytochrome c oxidase mRNA and protein in a mouse macrophage cell line
AU - Lehrer-Graiwer, Joshua E.
AU - Firestein, Bonnie L.
AU - Bredt, David S.
N1 - Funding Information:
J.L.G. was supported by a grant from the American Heart Association, and B.F. was supported by a grant from the Spinal Cord Research Foundation. This research was supported by grants (to D.S.B.) from the NIH (RO1-NS34822), the National Association for Research on Schizophrenia and Depression, and the Culpeper and Beckman Foundations.
PY - 2000/7/14
Y1 - 2000/7/14
N2 - Neurons that express neuronal nitric oxide synthase (nNOS) are selectively spared from nitric oxide (NO)-induced cytotoxicity in acute cerebral ischemia and neurodegenerative conditions but the mechanism of this resistance is unknown. To identify specific gene products which may mediate this resistance, we performed polymerase chain reaction (PCR)-based subtractive hybridization on a mouse macrophage cell line treated with either L-NG-nitroarginine methyl ester (L-NAME, 1 mM, 1 h), an inhibitor of NOS, or with diethylamine NONOate (DEA NONO, 200 μM, 1 h), an NO donor. NO-treated cultures showed an acute induction of mRNA (less than 1 h after treatment) and protein (15 min) for the mitochondrial enzyme cytochrome c oxidase (CcO) as shown by Northern or Western blot analysis, respectively. Cytochrome c oxidase activity assay showed constant activity in NO-treated cultures, as compared to L-NAME-treated cultures. NO directly inhibits CcO, the terminal electron acceptor in mitochondrial oxidative respiration. Up-regulation of this enzyme by NO, therefore, appears to maintain vital CcO activity and cellular energy stores, thus contributing to selective sparing of nNOS neurons. Copyright (C) 2000 Elsevier Science Ireland Ltd.
AB - Neurons that express neuronal nitric oxide synthase (nNOS) are selectively spared from nitric oxide (NO)-induced cytotoxicity in acute cerebral ischemia and neurodegenerative conditions but the mechanism of this resistance is unknown. To identify specific gene products which may mediate this resistance, we performed polymerase chain reaction (PCR)-based subtractive hybridization on a mouse macrophage cell line treated with either L-NG-nitroarginine methyl ester (L-NAME, 1 mM, 1 h), an inhibitor of NOS, or with diethylamine NONOate (DEA NONO, 200 μM, 1 h), an NO donor. NO-treated cultures showed an acute induction of mRNA (less than 1 h after treatment) and protein (15 min) for the mitochondrial enzyme cytochrome c oxidase (CcO) as shown by Northern or Western blot analysis, respectively. Cytochrome c oxidase activity assay showed constant activity in NO-treated cultures, as compared to L-NAME-treated cultures. NO directly inhibits CcO, the terminal electron acceptor in mitochondrial oxidative respiration. Up-regulation of this enzyme by NO, therefore, appears to maintain vital CcO activity and cellular energy stores, thus contributing to selective sparing of nNOS neurons. Copyright (C) 2000 Elsevier Science Ireland Ltd.
KW - Apoptosis
KW - Cytochrome c oxidase
KW - Mitochondria
KW - Neurotoxicity
KW - Nitric oxide
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U2 - 10.1016/S0304-3940(00)01205-2
DO - 10.1016/S0304-3940(00)01205-2
M3 - Article
C2 - 10876072
AN - SCOPUS:0034648103
SN - 0304-3940
VL - 288
SP - 107
EP - 110
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -