Acta Pharmacologica Sinica 2007 August; 28 (8): 1097-1104; doi: 10.1111/j.1745-7254.2007.00624.x

 
Original Article
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Greater stress protein expression enhanced by combined prostaglandin A1 and lithium in a rat model of focal ischemia1
 

Xi-hui XU2,3, Yi-nan HUA2,3, Hui-ling ZHANG2,3, Jun-chao WU2,3, You-zhu MIAO2,3, Rong HAN2,3, Zhen-lun GU2,3, Zheng-hong QIN2,3,4

2Laboratory of Aging and Nervous Disease and 3Department of Pharmacology, Soochow University School of Medicine, Suzhou 215123, China

 

Aim: 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), HSP90a, and Apaf-1 were significantly increased, but the expression of HSP90b 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 HSP90α, and recovered HSP90β expression, but decreased Apaf-1 levels in the ischemic striatum.


Conclusion:
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.

 

Keywords: prostaglandin A1; lithium; oxidative stress; heat shock factor 1; cerebral ischemia; Apaf-1; HO-1; HSP90α; HSP90β

 
1 Project supported by grants from the Depart- ment of Education of Jiangsu Province (No 03KJB310123), the Natural Science Founda-tion of Jiangsu Province (No BK2004037), and the National Natural Science Foundation of China (No 30470587).

4 Correspondence to Prof Zheng-hong QIN.
Phn/Fax 86-512-6588-0406.
E-mail zhqin5@hotmail.com
Received 2006-11-09     Accepted 2006-12-21

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