title: Probucol inhibits neural cell apoptosis via inhibition of mTOR signaling pathway after spinal cord injury.
abstract: Autophagy plays an essential role in neurodevelopment, axonal guidance, neuropathic pain remission, and neuronal survival. Inhibiting the mammalian target of rapamycin (mTOR) signaling pathway can induce the occurrence of autophagy. In this study, we initially detected the effect of probucol on autophagy after spinal cord injury (SCI) by intraperitoneally injecting spinal cord-injured rats with probucol for 7days. The levels of Beclin1 and LC3B were evidently enhanced at 7days post-operation. However, the increase in the phosphorylated AMP-activated protein kinase (AMPK) protein and the decrease in ribosomal protein S6 kinase p70 subtype (p70S6K) phosphorylation level simultaneously occurred after SCI. Moreover, the expression levels of apoptosis-related proteins of Caspase-3, Caspase-9, and Bax were significantly reduced. Immunofluorescence results indicated that the expression of Caspase-3 protein was evidently decreased and that of Beclin-1 protein was increased by probucol. Nissl staining and Basso, Beattie, and Bresnahan scores showed that the quantity and function of motor neurons were visibly preserved by probucol after SCI. This study showed that probucol inhibited the mTOR signaling pathway to induce autophagy, reduce neural cell apoptosis and promote recovery of neurological function after SCI.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Jinzhou Medical University, Jinzhou, China.
authors.forename: Shurui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Haosen
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Second Hospital of Jinzhou, Jinzhou, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. Electronic address: meixifan1971@163.com.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D011341:Probucol
keywords: apoptosis; autophagy; mTOR; probucol; spinal cord injury