Greater stress protein expression enhanced by combined prostaglandin A1 and lithium in a rat model of focal ischemia.
OBJECTIVE
To investigate the effects of lithium (Li) and prostaglandin A1 (PGA1) on the expression of heat shock factor 1 (HSF-1), heat shock proteins (HSP), and apoptosis protease activating factor-1 (Apaf-1) induced by permanent focal ischemia in rats.


METHODS
The rats were pretreated with a subcutaneous (sc) injection of Li for 2 d or a single intracerebral ventricle (icv) administration of PGA1 for 15 min before ischemic insult, or a combination of Li (sc, 1 mEq/kg, 2 d) and PGA1 (icv, 15 min prior to ischemic insult). Brain ischemia was induced by the permanent middle cerebral artery occlusion (pMCAO). Twenty-four hours after the occlusion, the expression of HSF-1, HSP, and Apaf-1 in the ischemic striatum were examined with Western blot analysis.


RESULTS
The expression of HSF-1, heme oxygenase-1 (HO-1), HSP90alpha, and Apaf-1 were significantly increased, but the expression of HSP90beta was significantly decreased 24 h after the pMCAO. PGA1 and Li and their combination significantly enhanced the ischemia-induced elevation in the levels of HSF-1, HO-1, and HSP90alpha, and recovered HSP90beta expression, but decreased Apaf-1 levels in the ischemic striatum.


CONCLUSIONS
The present study demonstrates that PGA1 and Li have synergistic effects on the enhancement of the expression of HSP, suggesting that the synergistic effects of PGA1 and Li in the rat model of permanent focal cerebral ischemia may be mediated by the enhancement expression of HSP expression and the downregulation of Apaf-1. Our studies suggest that combined PGA1 and Li may have potential clinical value for the treatment of stroke.
Xu
Xi-hui
XH
Laboratory of Aging and Nervous Disease, Soochow University School of Medicine, Suzhou, China.
Hua
Yi-nan
YN
Zhang
Hui-ling
HL
Wu
Jun-chao
JC
Miao
You-zhu
YZ
Han
Rong
R
Gu
Zhen-lun
ZL
Qin
Zheng-hong
ZH
D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1 / Q000037:antagonists & inhibitors; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis*; D000076249:Heat Shock Transcription Factors; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011454:Prostaglandins A / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis*
C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D011454:Prostaglandins A; D014157:Transcription Factors; D008094:Lithium; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C100573:prostaglandin A1