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Nitric oxide signaling: a possible role for G proteins
H M Lander1, P K Sehajpal, A Novogrodsky
1Rogosin Institute, Cornell University Medical College, New York, NY 10021.
Journal of Immunology (Baltimore, Md. : 1950)
|December 15, 1993
Summary
Nitric oxide directly activates guanine nucleotide-binding proteins (G proteins) in human immune cells. This novel signaling pathway influences immune responses and may be a target for new therapies.
Area of Science:
- Immunology
- Cellular signaling
- Molecular biology
Background:
- Nitric oxide (NO) is known to induce effects on human peripheral blood mononuclear cells (PBMCs).
- The precise mechanisms of NO signaling are still being elucidated.
- Guanine nucleotide-binding proteins (G proteins) are critical regulators of numerous cellular processes.
Purpose of the Study:
- To investigate a novel mechanism of nitric oxide signaling through direct activation of G proteins.
- To explore the functional consequences of NO-mediated G protein activation in human PBMCs.
Main Methods:
- Treatment of isolated human PBMC membranes and whole cells with nitric oxide.
- Assays for GTPase activity and GTP binding using radiolabeled GTP.
- Analysis of recombinant G protein activity (Gs alpha, Gi alpha 1, p21ras).
- Inhibition studies using GDP-beta-S and pertussis toxin.
Main Results:
- Nitric oxide treatment enhanced GTPase activity and GTP binding in PBMC membranes.
- NO increased GTPase activity in isolated recombinant G proteins (Gs alpha, Gi alpha 1, p21ras).
- G protein inhibition blocked NO-induced NF-kappa B translocation, and NO reduced pertussis toxin-mediated ADP-ribosylation.
Conclusions:
- Nitric oxide directly activates G proteins, representing a novel signaling pathway.
- This NO-G protein interaction plays a role in cellular responses within human PBMCs.
- Activation of G proteins by an endogenous oxidant offers a new perspective on cellular communication.