Autophagy following heat stress: The role of aging and protein nitration

Abstract

Stress can originate from a variety of sources (e.g. physical, chemical, etc.) and cause protein denaturation, DNA damage, and possibly death. In an effort to prevent such deleterious consequences, most organisms possess one or more ways to counteract or even prevent the harmful effect(s) from a given stressor. Such compensation by an organism is known as a stress response; this involves inhibition of housekeeping genes and subsequent activation of genes associated with the stress response.1 One of the most widely studied groups of stress response genes is a family of molecular chaperones known as heat shock proteins (HSPs). Work from our laboratory agrees with many other studies showing an age-related decline in stress-induced synthesis of HSPs.2 A decline in the availability and/or function of HSPs with age can lead to accumulation of damaged proteins, which in turn damages cells. Recently, our laboratory found a significant increase in mitochondrial damage as well as evidence of increased autophagy in rat hepatocytes following heat stress.3 These results, along with findings of increased protein nitration with age, suggest a major role for reactive nitrogen species (RNS) in both the decline in HSP induction and increased hepatocyte pathology observed in old rats following heat stress. Addendum to: Oberley TD, Swanlund JM, Zhang HJ, Kregel KC. Aging results in increased autophagy of mitochondria and protein nitration in rat hepatocytes following heat stress. J Histochem Cytochem 2008; 56:615-27.