Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways.
Minocycline, a semi-synthetic second-generation derivative of tetracycline, has been reported to exert neuroprotective effects both in animal models and in clinic trials of neurological diseases. In the present study, we first investigated the protective effects of minocycline on oxygen-glucose deprivation and reoxygenation-induced impairment of neurite outgrowth and its potential mechanism in the neuronal cell line, PC12 cells. We found that minocycline significantly increased cell viability, promoted neurite outgrowth and enhanced the expression of growth-associated protein-43 (GAP-43) in PC12 cells exposed to oxygen-glucose deprivation/reoxygenation injury. In addition, immunoblots revealed that minocycline reversed the overexpression of phosphorylated myosin light chain (MLC) and the suppression of activated extracellular signal-regulated kinase 1/2 (ERK1/2) caused by oxygen-glucose deprivation/reoxygenation injury. Moreover, the minocycline-induced neurite outgrowth was significantly blocked by Calyculin A (1 nM), an inhibitor of myosin light chain phosphatase (MLCP), but not by an ERK1/2 inhibitor (U0126; 10 μM). These findings suggested that minocycline activated the MLCP/MLC signaling pathway in PC12 cells after oxygen-glucose deprivation/reoxygenation injury, which resulted in the promotion of neurite outgrowth.
Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 64600, Sichuan Province, China.
Tao
T
Tao
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Jin-Zhou
JZ
Feng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Guang-Hui
GH
Xu
Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 64600, Sichuan Province, China.
Jie
J
Fu
Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 64600, Sichuan Province, China.
Xiao-Gang
XG
Li
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. qinxinyue@sina.com.
Xin-Yue
XY
Qin
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019922:GAP-43 Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D008911:Minocycline / Q000494:pharmacology*; D018994:Myosin Light Chains / Q000378:metabolism*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
D019922:GAP-43 Protein; D018994:Myosin Light Chains; D048049:Extracellular Signal-Regulated MAP Kinases; D043263:Myosin-Light-Chain Phosphatase; D008911:Minocycline; D005947:Glucose; D010100:Oxygen
Minocycline; Myosin light chain; Neurite outgrowth; Oxygen-glucose deprivation and reoxygenation; PC12 cells