Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2  inhibitor

doi:10.3969/j.issn.1673-5374.2012.34.008

Neural Regeneration Research ›› 2012, Vol. 7 ›› Issue (34): 2705-2712.doi: 10.3969/j.issn.1673-5374.2012.34.008

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Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor

Weigang Duan¹, Ling Que¹, Xiaoman Lv¹, Qifeng Li¹, Hua Yin¹, Luyong Zhang²

1 Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan Province, China
2 New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Received:2012-02-06 Revised:2012-07-24 Online:2012-12-05 Published:2012-07-24
Contact: Weigang Duan, Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan Province, China deardwg@126.com
About author:Weigang Duan☆, M.D., Associate professor, Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan Province, China
Supported by:
This study was financially supported by Yunnan Provincial Science and Technology Department, No. 2009CD079 and by the National Natural Science Foundation of China, No. 81060109.

Abstract

Abstract:

In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors (Y27632 and Fasudil), a cyclooxygenase-1 selective inhibitor (SC560), and a cyclooxygenase-2 inhibitor (NS398). We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance.

Key words: Rho-associated kinase inhibitors, Y27632, fasudil, neurite, cyclooxygenase 2 inhibitors, drug tolerance

Weigang Duan, Ling Que, Xiaoman Lv, Qifeng Li, Hua Yin, Luyong Zhang. Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor[J]. Neural Regeneration Research, 2012, 7(34): 2705-2712.

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Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor

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