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 mucosal damage caused by aspirin during repeated long-term administration of aspirin. However, the underlying mechanism of this adaptation is not well established. In the present study, we investigated the effect of long-term (chronic) administration of aspirin on expression of heat shock proteins (HSPs), which are known as endogenous cytoprotectants, in rat gastric mucosa. Rats were administered aspirin (100 mg/kg) daily for up to 20 days. After various 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. Intracellular localization of each HSP was studied immunohistochemically. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels were also investigated. Long-term aspirin administration resulted in development of resistance to aspirin-induced mucosal damage, and the increase of HSP72 expression correlated with mucosal resistance to aspirin. No significant increase was observed in HSP60 and HSP90 levels. Immunohistochemical study showed an increase of HSP72 in the cytoplasm of mucosal surface cells. The PGE2 level was suppressed and no change in the level of LTB4 was observed. It is possible that HSP72 could play important roles in gastric mucosal adaptation when the PGE2 level is suppressed by NSAIDs.
Jin
M
M
First Department of Internal Medicine, Akita University School of Medicine, Hondo, Akita City, Japan.
Otaka
M
M
Okuyama
A
A
Itoh
S
S
Otani
S
S
Odashima
M
M
Iwabuchi
A
A
Konishi
N
N
Wada
I
I
Pacheco
I
I
Itoh
H
H
Tashima
Y
Y
Masamune
O
O
Watanabe
S
S
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity*; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics*; D007124:Immunoenzyme Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D008134:Long-Term Care; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007975:Leukotriene B4; D015232:Dinoprostone; D001241:Aspirin