Direct Rho-associated kinase inhibiton induces cofilin dephosphorylation and neurite outgrowth in PC-12 cells

Cellular & Molecular Biology Letters

Kevin K. W. Wang²  Stephen F. Larner⁴  Zhiqun Zhang³  Andrew K. Ottens³  Ronald L. Hayes⁵  Melissa L. Williams¹  Firas H. Kobeissy³ 

[1] Departments of Neuroscience, University of Florida, Gainesville, USA$$;Centers for Neuroproteomics and Biomarkers Research, University of Florida, Gainesville, USA$$Traumatic Brain Injury Studies, University of Florida, Gainesville, USA$$Departments of Neuroscience, University of Florida, Gainesville, USA$$Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, USA$$;Centers for Neuroproteomics and Biomarkers Research, University of Florida, Gainesville, USA$$Traumatic Brain Injury Studies, University of Florida, Gainesville, USA$$Departments of Neuroscience, University of Florida, Gainesville, USA$$;Traumatic Brain Injury Studies, University of Florida, Gainesville, USA$$Departments of Neuroscience, University of Florida, Gainesville, USA$$;Traumatic Brain Injury Studies, University of Florida, Gainesville, USA$$Departments of Neuroscience, University of Florida, Gainesville, USA$$Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, USA$$

关键词: Neurite outgrowth;    ROCK;    Y-27632;    PC-12;    Cofilin;    Actin dynamics;   

DOI  :  10.2478/s11658-006-0002-x

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Axons fail to regenerate in the adult central nervous system (CNS) following injury. Developing strategies to promote axonal regeneration is therapeutically attractive for various CNS pathologies such as traumatic brain injury, stroke and Alzheimer’s disease. Because the RhoA pathway is involved in neurite outgrowth, Rho-associated kinases (ROCKs), downstream effectors of GTP-bound Rho, are potentially important targets for axonal repair strategies in CNS injuries. We investigated the effects and downstream mechanisms of ROCK inhibition in promoting neurite outgrowth in a PC-12 cell model. Robust neurite outgrowth (NOG) was induced by ROCK inhibitors Y-27632 and H-1152 in a time-and dose-dependent manner. Dramatic cytoskeletal reorganization was noticed upon ROCK inhibition. NOG initiated within 5 to 30 minutes followed by neurite extension between 6 and 10 hours. Neurite processes were then sustained for over 24 hours. Rapid cofilin dephosphorylation was observed within 5 minutes of Y-27632 and H-1152 treatment. Re-phosphorylation was observed by 6 hours after Y-27632 treatment, while H-1152 treatment produced sustained cofilin dephosphorylation for over 24 hours. The results suggest that ROCK-mediated dephosphorylation of cofilin plays a role in the initiation of NOG in PC-12 cells.

【 授权许可】

Unknown