Altered accumulation of hepatic mitochondrial antioxidant proteins with age and environmental heat stress.

Abstract

Aging impairs overall physiological function, particularly the response to environmental stressors. Repeated heat stress elevates reactive oxygen species and macromolecular damage in the livers of aged animals, likely due to mitochondrial dysfunction. The goal of this investigation was to determine potential mechanisms for mitochondrial dysfunction after heat stress by evaluating key redox-sensitive and antioxidant proteins (Sirt-3, MnSOD, Trx-2, and Ref-1). We hypothesized that heat stress would result in greater mitochondrial abundance of these proteins, but that aging would attenuate this response. For this purpose, young (6 mo) and old (24 mo) Fisher 344 rats were exposed to heat stress on two consecutive days. During each heating trial, colonic temperature was elevated to 41°C during the first 60 min, and then clamped at this temperature for 30 min. Nonheated animals served as controls. At 2 and 24 h after the second heat stress, hepatic mitochondria were isolated from each animal, and then immunoblotted for Sirt-3, acetylated lysine residues (Ac-K), MnSOD, Trx-2, and Ref-1. Aging increased Sirt-3 and lowered Ac-K. In response to heat stress, Sirt-3, Ac-K, MnSOD, and Ref-1 increased in mitochondrial fractions in both young and old animals. At 2 h after the second heat stress, mitochondrial Trx-2 declined in old, but not in young animals. Our results suggest that some components of the response to heat stress are preserved with aging. However, the decline in Trx-2 represents a potential mechanism for age-related mitochondrial damage and dysfunction after heat stress.NEW & NOTEWORTHY Our results suggest heat stress-induced mitochondrial translocation of Sirt-3, MnSOD, and Ref-1 in young and old animals. Aged rats experienced a decline in Trx-2 after heat stress, suggesting a potential mechanism for age-related mitochondrial dysfunction.