Differential expression of heme oxygenase‐1 in young and old rats after heat stress

Heme oxygenase‐1 (HO‐1) plays an important role in protecting cells from multiple stresses. This study was designed to determine the effects of heat stress on HO‐1 protein expression in young (6 mo) and old (24 mo) rats. Rats were subjected to two heats separated by 24 h. Livers were harvested between 0 and 24 h after the second heating and HO‐1 expression was analyzed by western blot and immunohistochemistry (IHC). Immunoblots showed higher levels of HO‐1 protein in livers of old rats compared to young rats under sham heated conditions. HO‐1 was further induced by heat stress in the old rats, while young rats demonstrated an increase in HO‐1 expression at early time points and then a return to control levels at 24 h post‐heating. IHC analysis demonstrated that the expression of HO‐1 is predominately in Kupffer cells in both young and old livers. Under sham heated conditions, the old rats displayed more HO‐1 ‐ positive cells than the young rats. The number of cells that stained for HO‐1 did not increase in old livers after heating; however, an increase in HO‐1‐ positive cells was observed in young livers at both 2 and 24 h post heating. These results may suggest an effect of age on individual cell expression of HO‐1 or the total number of Kupffer cells within the liver. Separate groups of rats were treated with gadolinium chloride (GC), an inhibitor of Kupffer cell phagocytosis, 24 h prior to the first heating. GC treatment reduced the number of HO‐1 stained cells in young but not old rats. These data suggest differential regulation of HO‐1 expression between young and old animals, which may be an important mechanism of reduced stress tolerance in old organisms. NIH AG 12350.