The Adaptive Response to Intestinal Oxidative Stress in Mammalian Hibernation
Abstract
The goal of this project is demonstrate how mammalian hibernators utilize the physiologic consequences of metabolic depression, which include changes in mitochondrial function, low body temperatures (T sub b) and reduced blood flow, to activate cellular signaling pathways that minimize oxidative damage to sensitive tissues during torpor-arousal cycles. Specific Aim 1 examines oxidative stress to the gut of ground squirrels during the seasonal cycle. (a) accumulation of oxidized lipids in the intestine (in progress); (b) seasonal changes in the intestinal glutathione redox system (completed); (c) seasonal changes in intestinal antioxidant enzymes (in progress). Specific Aim 2 examines consequences of intestinal oxidative stress during hibernation. a) seasonal changes in NF-Kappa(B) activation in intestine and the identity of activated cells (completed); b) seasonal changes in the intestinal mucosal immune system (in progress); c) the effect of hibernation on enterocyte apoptosis and cell cycle regulators (in progress). Part c has already identified several pro-and anti-apototic pathways as well as cell cycle proteins that are activated in the gut during hibernation. We have also completed studies on protein ubiquitination and the response of the exocrine pancreas to hibernation. Other studies related to the main goal of the project are in progress, including development of an intestinal ischemia-reperfusion model to test the protective effects of the hibernation phenotype on this trauma-induced event. Our findings provide insight into the dynamic nature of the hibernating phenotype in terms of oxidative stress and development of antioxidant defenses during regulated hypothermia and hypometabolism, and contribute to our working model of "natural preconditioning" in mammalian hibernators.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 24, 2003
- Accession Number
- ADA424599
Entities
People
- Hannah V. Carey
Organizations
- University of Wisconsin–Madison