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Related Experiment Videos

Nitric oxide activates diverse signaling pathways to regulate gene expression.

Jill Hemish1, Naoki Nakaya, Vivek Mittal

  • 1Cold Spring Harbor Laboratory, 1 Bungtown Road, PO Box 100, Cold Spring Harbor, NY 11724, USA.

The Journal of Biological Chemistry
|August 9, 2003
PubMed
Summary

Nitric oxide (NO) triggers distinct gene activity waves in cells, revealing its complex signaling. These waves are mediated by multiple independent pathways, including those involving p53 and NF-kappaB.

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Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Genomics

Background:

  • Nitric oxide (NO) is a critical signaling molecule involved in various cellular processes.
  • Understanding the temporal dynamics and signaling pathways of NO-induced gene expression is essential.

Purpose of the Study:

  • To elucidate the temporal order of gene activation by NO in mammalian cells.
  • To identify the specific signaling pathways mediating NO's effects on gene expression.

Main Methods:

  • Gene expression kinetics were analyzed using microarrays and quantitative real-time PCR.
  • Pharmacological inhibitors and genetic approaches (p53 knockout cells) were employed to dissect signaling pathways.
  • Endogenous NO production was induced using cytokines for validation.

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Main Results:

  • NO induces a triphasic pattern of gene activation, with distinct early and later waves.
  • The initial wave of gene activity represents primary NO targets, followed by secondary cascades.
  • Specific signaling pathways, including phosphatidylinositol 3-kinase, protein kinase C, NF-kappaB, and p53, were identified as mediators of NO-induced gene expression.

Conclusions:

  • Nitric oxide orchestrates gene expression through a complex, temporally regulated cascade.
  • Multiple, independent signaling pathways are utilized by NO to achieve its diverse cellular effects.