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Neurite outgrowth resistance to rho kinase inhibitors in PC12 Adh cell
Authors:Hua Yin  Xiaolin Hou  Tingrui Tao  Xiaoman Lv  Luyong Zhang  Weigang Duan
Affiliation:1. Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Traditional Chinese Medicine, Kunming, China;2. Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China;3. Initiative team of Microenvironment, Yunnan Key Laboratory for Enthnomedicine, Chenggong District, Kunming, China
Abstract:Rho kinase (ROCK) inhibitor is a promising agent for neural injury disorders, which mechanism is associated with neurite outgrowth. However, neurite outgrowth resistance occurred when PC12 Adh cell was treated with ROCK inhibitors for a longer time. PC12 Adh cells were treated with ROCK inhibitor Y27632 or NGF for different durations. Neurite outgrowth resistance occurred when PC12 Adh cell exposed to Y27632 (33 µM) for 3 or more days, but not happen when exposed to nerve growth factor (NGF, 100 ng/mL). The gene expression in the PC12 Adh cells treated with Y27632 (33 µM) or NGF (100 ng/mL) for 2 or 4 days was assayed by gene microarray, and the reliability of the results were confirmed by real‐time RT‐PCR. Cluster analysis proved that the gene expression profile of PC12 Adh cell treated with Y27632 for 4 days was different from that treated with Y27632 for 2 days and those treated with NGF for 2 and 4 days, respectively. Pathway analysis hinted that the neurite outgrowth resistance could be associated with up‐regulation of inflammatory pathways, especially rno04610 (complement and coagulation cascades), and down‐regulation of cell cycle pathways, especially rno04110.
Keywords:cell differentiation  neurite outgrowth resistance  PC12 Adh cell  rho kinase inhibitor  Y27632
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