title: Neurite outgrowth resistance to rho kinase inhibitors in PC12 Adh cell.
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.
authors.affiliation: Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Traditional Chinese Medicine, 1076, Yuhua Road, University City of Chenggong, Kunming, 650500, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yin
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hou
authors.forename: Tingrui
authors.initials: T
authors.lastname: Tao
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Lv
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Weigang
authors.initials: W
authors.lastname: Duan
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D046228:Microarray Analysis; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000235:genetics; D016716:PC12 Cells; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; C502240:NGF protein, human; D011725:Pyridines; C108830:Y 27632; D020932:Nerve Growth Factor; D054460:rho-Associated Kinases
keywords: PC12 Adh cell; Y27632; cell differentiation; neurite outgrowth resistance; rho kinase inhibitor