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Endotoxin-stimulated nitric oxide production inhibits expression of cytochrome c oxidase in ANA-1 murine macrophages.

Publication ,  Journal Article
Wei, J; Guo, H; Kuo, PC
Published in: J Immunol
May 1, 2002

In endotoxin (LPS)-mediated states of sepsis, inducible NO synthase expression and NO production are associated with molecular regulatory functions that determine the host inflammatory response. NO inhibits cellular respiration and mitochondrial electron transport by inhibition of cytochrome c oxidase (CcO) activity. CcO is the terminal complex of the mitochondrial respiratory chain, responsible for 90% of cellular oxygen consumption and essential for cellular energy production. Subunit 1 (CcO I) is considered to be the most critical of the 13 CcO component subunits. In this regard little is known of the effect of NO on the transcriptional program for CcO expression. In ANA-1 murine macrophages, LPS-mediated NO synthesis decreases CcO enzyme activity, CcO I protein expression, and CcO I steady mRNA levels. Mitochondrial run-on analysis demonstrates unaltered CcO I mitochondrial gene transcription. Half-life analysis indicates that CcO I mRNA stability is significantly decreased in the presence of LPS-mediated NO synthesis. In this study using LPS-stimulated ANA-1 murine macrophages, we demonstrate that expression of the mitochondrial gene product, CcO I, is significantly decreased as the result of a unique and previously uncharacterized, NO-dependent post-transcriptional regulatory mechanism.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2002

Volume

168

Issue

9

Start / End Page

4721 / 4727

Location

United States

Related Subject Headings

  • RNA, Mitochondrial
  • RNA, Messenger
  • RNA Stability
  • RNA
  • Nitric Oxide
  • Mitochondrial Proteins
  • Mice
  • Macrophages
  • Lipopolysaccharides
  • Immunology
 

Citation

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Wei, J., Guo, H., & Kuo, P. C. (2002). Endotoxin-stimulated nitric oxide production inhibits expression of cytochrome c oxidase in ANA-1 murine macrophages. J Immunol, 168(9), 4721–4727. https://doi.org/10.4049/jimmunol.168.9.4721
Wei, Junping, Hongtao Guo, and Paul C. Kuo. “Endotoxin-stimulated nitric oxide production inhibits expression of cytochrome c oxidase in ANA-1 murine macrophages.J Immunol 168, no. 9 (May 1, 2002): 4721–27. https://doi.org/10.4049/jimmunol.168.9.4721.
Wei, Junping, et al. “Endotoxin-stimulated nitric oxide production inhibits expression of cytochrome c oxidase in ANA-1 murine macrophages.J Immunol, vol. 168, no. 9, May 2002, pp. 4721–27. Pubmed, doi:10.4049/jimmunol.168.9.4721.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2002

Volume

168

Issue

9

Start / End Page

4721 / 4727

Location

United States

Related Subject Headings

  • RNA, Mitochondrial
  • RNA, Messenger
  • RNA Stability
  • RNA
  • Nitric Oxide
  • Mitochondrial Proteins
  • Mice
  • Macrophages
  • Lipopolysaccharides
  • Immunology