Association of 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa

It is well documented that gastric mucosa can increase its resistance to mu cosal damage caused by aspirin during repeated long-term administration of aspirin. However, the underlying mechanism of this adaptation is not well e stablished. In the present study, we investigated the effect of long-term ( chronic) administration of aspirin on expression of heat shock proteins (HS Ps), which are known as endogenous cytoprotectants, in rat gastric mucosa. Rats were administered aspirin (100 mg/kg) daily for up to 20 days. After v arious periods of aspirin administration, a high dose of aspirin (250 mg/kg ) was administered, and the mucosal damage was assessed. Expression of heat shock proteins (HSPs) in gastric mucosa was evaluated by Western blot. Int racellular localization of each HSP was studied immunohistochemically. Pros taglandin E-2 (PGE(2)) and leukotriene B-4 (LTB4) levels were also investig ated. Long-term aspirin administration resulted in development of resistanc e to aspirin-induced mucosal damage, and the increase of HSP72 expression c orrelated with mucosal resistance to aspirin. No significant increase was o bserved in HSP60 and HSP90 levels. Immunohistochemical study showed an incr ease of HSP72 in the cytoplasm of mucosal surface cells. The PGE(2) level w as suppressed and no change in the level of LTB4 was observed. It is possib le that HSP72 could play important roles in gastric mucosal adaptation when the PGE(2) level is suppressed by NSAIDs.