PMID- 10876072 OWN - NLM STAT- MEDLINE DCOM- 20001010 LR - 20190701 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 288 IP - 2 DP - 2000 Jul 14 TI - Nitric oxide mediated induction of cytochrome c oxidase mRNA and protein in a mouse macrophage cell line. PG - 107-10 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 microM, 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. FAU - Lehrer-Graiwer, J E AU - Lehrer-Graiwer JE AD - Department of Physiology, University of California at San Francisco School of Medicine, 513 Parnassus Avenue, 94143-0444, San Francisco, CA, USA. FAU - Firestein, B L AU - Firestein BL FAU - Bredt, D S AU - Bredt DS LA - eng GR - R01-NS34822/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (RNA, Messenger) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Animals MH - Cell Line MH - Electron Transport Complex IV/*biosynthesis/genetics MH - Enzyme Induction/genetics MH - Macrophages/*enzymology MH - Mice MH - Nitric Oxide/*physiology MH - Nucleic Acid Hybridization MH - RNA, Messenger/*biosynthesis MH - Up-Regulation/genetics EDAT- 2000/07/06 11:00 MHDA- 2000/10/14 11:01 CRDT- 2000/07/06 11:00 PHST- 2000/07/06 11:00 [pubmed] PHST- 2000/10/14 11:01 [medline] PHST- 2000/07/06 11:00 [entrez] AID - S0304-3940(00)01205-2 [pii] AID - 10.1016/s0304-3940(00)01205-2 [doi] PST - ppublish SO - Neurosci Lett. 2000 Jul 14;288(2):107-10. doi: 10.1016/s0304-3940(00)01205-2.