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Activation of Rac1-dependent redox signaling is critically involved in staurosporine-induced neurite outgrowth in PC12 cells

Authors
 Du Sik Kim  ;  Jeong Mi An  ;  Han Gil Lee  ;  Su Ryeon Seo  ;  Seon Sook Kim  ;  Ju Yeon Kim  ;  Jeong Wan Kang  ;  Yun Soo Bae  ;  Jeong Taeg Seo 
Citation
 Free Radical Research, Vol.47(2) : 95-103, 2013 
Journal Title
 Free Radical Research 
ISSN
 1071-5762 
Issue Date
2013
Abstract
Staurosporine, a non-specific protein kinase inhibitor, has been shown to induce neurite outgrowth in PC12 cells, but the mechanism by which staurosporine induces neurite outgrowth is still obscure. In the present study, we investigated whether the activation of Rac1 was responsible for the neurite outgrowth triggered by staurosporine. Staurosporine caused rapid neurite outgrowth independent of the ERK signaling pathways. In contrast, neurite outgrowth in response to staurosporine was accompanied by activation of Rac1, and the Rac1 inhibitor NSC23766 attenuated the staurosporine-induced neurite outgrowth in a concentration-dependent manner. In addition, suppression of Rac1 activity by expression of the dominant negative mutant Rac1N17 also blocked the staurosporine-induced morphological differentiation of PC12 cells. Staurosporine caused an activation of NADPH oxidase and increased the production of reactive oxygen species (ROS), which was prevented by NSC23766 and diphenyleneiodonium (DPI), an NADPH oxidase inhibitor. Staurosporine-induced neurite outgrowth was attenuated by pretreatment with DPI and exogenous addition of sublethal concentration of H2O2 accelerated neurite outgrowth triggered by staurosporine. These results indicate that activation of Rac1, which leads to ROS generation, is required for neurite outgrowth induced by staurosporine in PC12 cells.
Full Text
http://informahealthcare.com/doi/abs/10.3109/10715762.2012.748193
DOI
10.3109/10715762.2012.748193
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Jeong Wan(강정완) ORCID logo https://orcid.org/0000-0002-3945-8452
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86342
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