PROTEIN TYROSINE NITRATION: A MEMBRANE-ORGANIZED MECHANISM FOR ALTERED SIGNAL TRANSDUCTION DURING PROINFLAMMATORY STRESS

Authors: Elsasser, Theodore; Kahl, Stanislaw; SARTIN, J. - AUBURN UNIVERSITY; Li, Congjun - Cj

Submitted to: American Society of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: 5/31/2004
Publication Date: 6/1/2004
Citation: Elsasser, T.H., Kahl, S., Sartin, J.L., Li, C. 2004. Protein tyrosine nitration: a membrane organized mechanism for altered signal transduction during proinflammatory stress [abstract]. Journal of Animal Science 82 (Suppl.1):445.

Interpretive Summary:

Technical Abstract: Three constitutive isoforms of nitric oxide synthase (NOS), ie., endothelial-, neuronal-, and mitochondrial (a fourth isoform being the high-output inducible form), impact physiological processes through their respective localized low-output production of nitric oxide from arginine. Their activities are regulated through specific phosphorylations and co-factor interactions. A significant feature of NO-based cellular function resides in how NO is altered in association with the prevailing red-ox conditions within cells. Under minor anoxic conditions where tissue pCO2 increases concomitant generation of NO via NOS and superoxide anion via xanthine oxidase, can lead to the condensation of these free radicals to form the highly reactive oxynitrogen anion peroxynitrite (ONOO-). A major intracellular target for ONOO- is the phenolic ring of protein tyrosines where the attack results in the formation of nitrotyrosine. Nitrated proteins are identifiable the immunohistochemical localization of nitrotyrosine in a growing number of acute and chronic diseases. We have recently shown that nutrition is capable of modulating the development of protein nitration during low-level proinflammatory stress. Nutrition regulates NO production rates as well as provides a sink to alter the interaction of NO with intracellular components and 'mops-up' ONOO- via scavenging capabilities of '- and '-tocopherols. Most recently, however, we have identified membrane-based caveolae as sites of specific epitope-specific nitrations that appear to play a functional role in the acute modulation of signal transduction processes where, for example, the anabolic processes driven by the GH-IGF-1 axis need to be curtailed to facilitate alternative nutrient use paradigms for immunoresponse. Collectively, nutrient management of host response to immune challenge contributes significantly to how protein nitration reactions are managed and their study offers potential to develop intervention strategies to maintain animal health.