Herbimycin A attenuates apoptosis during heat stress in rats.
Expression of heat shock proteins (HSPs) as a heat stress response is associated with acquisition of thermotolerance. Herbimycin A is a tyrosine kinase inhibitor that has been shown to induce HSPs. The present study aims to investigate the effects of herbimycin A on thermotolerance in rats subjected to heat stress exposure. Herbimycin A induced hsp70 to peak levels 12 h post-injection in rats without heat stress. No change in hsp70 levels was observed in the vehicle- and saline-treated rats. In rats exposed to heat stress at 45 degrees C for 25 min, 12 h post-treatment, lower peak temperatures were attained in herbimycin A-treated group as compared to the vehicle- and saline-treated groups. Terminal transferase-mediated d-UTP nick end labeling (TUNEL) showed that a significant decrease in apoptosis of hepatocytes in herbimycin A-treated rats as compared to the vehicle- and saline-treated rats. Caspase-3 activation was also lower in herbimycin A-treated rats, compared to the vehicle- and saline-treated rats. The present study has demonstrated that herbimycin A is effective for development of thermotolerance and therefore protects rats from heat stress.
Sachidhanandam
Shankar B
SB
Department of Pharmacology, National University of Singapore, Singapore.
Lu
Jia
J
Low
Kerwin S Y
KS
Moochhala
Shabbir M
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018882:Heat Stress Disorders / Q000201:enzymology / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D047029:Lactams, Macrocyclic; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases