Effects of stress on endocrine and metabolic processes and redirection: Crosstalk between subcellular compartments

Authors: Elsasser, Theodore; Kahl, Stanislaw; Capuco, Anthony; Schmidt, Walter

Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2012
Publication Date: 5/1/2012
Citation: Elsasser, T.H., Kahl, S., Capuco, A.V., Schmidt, W.F. 2012. Effects of stress on endocrine and metabolic processes and redirection: Crosstalk between subcellular compartments. Domestic Animal Endocrinology. 43(2):132-145.

Interpretive Summary: The immune systems of animals suffering from bacterial infections generate many of the molecular compounds these animals need to combat the bacteria. However, if these compounds are overproduced, they can also injure the animal’s own tissues. Veterinarians need diagnostic tools that show which biochemical pathways may cause further injury to the sick animal so that better treatments can be provided. Our research indicates that computer models of how cellular proteins are altered by these reaction molecules can be used to predict what proteins are more likely to be harmed. By knowing where the affected proteins are located within the cell, scientists can suggest what therapies should be used to help the animal more rapidly recover from the disease.

Technical Abstract: Recent advances in genome analysis and biochemical pathway mapping have advanced our understanding of how biological systems have evolved over time. Protein and DNA marker comparisons suggest that several of these systems are both ancient in origin but highly conserved into today’s evolved species. However, remnants of some of the more ancient functions of these chemical systems can run in conflict with the functions that those same pathways serve in complex organisms and tissue systems today. Relevant to the present topic, nitric oxide (NO) and superoxide anion (SO), ancient cellular molecules in evolutionary terms, are recognized today as both necessary for the well-being and stable health of cells but also injurious to cells as elaborated in conjunction with the cellular stress response. Why the dichotomy? This question underlies one of the basic issues challenging researchers as well as practitioners in their approach to disease management where the fundamental proinflammatory response of the innate immune system of the host is needed for pathogen control but injurious to tissues from “collateral damage” from NO- and SO-derived reactive molecules. This review will highlight newer aspects of the biochemistry of the NO- and SO-mediated innate proinflammatory response and further illustrate how protein and tissue damage via overproduction of reactive nitrogen and oxygen intermediary molecules such as peroxynitrite might be targeted to specific epitopes of proteins. Based on the capacity to predict what proteins might be more or less affected by these post-translational chemical modifications to proteins in key locations in signal transduction and energy processing in the cell, scientists may be able to better suggest intervention strategies in the host response to a disease pathogen that is able to maintain the benefit of the innate immune response and limit the amount of “collateral damage” occurring to surrounding cells and tissues. Metabolic processes within subcellular compartments are discussed with regard to JAK-2-based signal transduction and mitochondrial function.