title: Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in rapid tolerance induced by electroacupuncture pretreatment through cannabinoid receptor type 1.
abstract: OBJECTIVE
  Our previous study has demonstrated that the rapid tolerance to cerebral ischemia by electroacupuncture (EA) pretreatment was possibly mediated through an endocannabinoid system-related mechanism. The purpose of this study was to investigate whether activation of epsilon protein kinase C (εPKC) was involved in EA pretreatment-induced neuroprotection via cannabinoid receptor type 1 in a rat model of transient focal cerebral ischemia.
  
  
  METHODS
  The activation of εPKC in the ipsilateral brain tissues after EA pretreatment was investigated in the presence or absence of cannabinoid receptor antagonists. At 2 hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in rats. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the expression of Bcl-2 and Bax were evaluated after reperfusion in the presence or absence of εPKC-selective peptide inhibitor (TAT-εV1-2) or activator (TAT-ψεRACK).
  
  
  RESULTS
  EA pretreatment enhanced εPKC activation. Systemic delivery of TAT-ψεRACK conferred neuroprotection against a subsequent cerebral ischemic event when delivered 2 hours before ischemia. Pretreatment with EA reduced infarct volumes, improved neurological outcome, inhibited neuronal apoptosis, and increased the Bcl-2-to-Bax ratio after reperfusion, and the beneficial effects were attenuated by TAT-εV1-2. In addition, the blockade of cannabinoid receptor type 1, but not cannabinoid receptor type 2 receptor, reversed the increase in εPKC activation and neuroprotection induced by EA pretreatment.
  
  
  CONCLUSIONS
  EA pretreatment may activate endogenous εPKC-mediated anti-apoptosis to protect against ischemic damage after focal cerebral ischemia via cannabinoid receptor type 1, which represents a new mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia in rats.
authors.affiliation: Department of Anesthesiology, Fourth Military Medical University, Shaanxi Province, China. wangqiang@fmmu.edu.cn
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xuying
authors.initials: X
authors.lastname: Li
authors.forename: Yanke
authors.initials: Y
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Qianzi
authors.initials: Q
authors.lastname: Yang
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Chen
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Min
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D015671:Electroacupuncture / Q000379:methods*; D004789:Enzyme Activation / Q000502:physiology; D008297:Male; D051744:Protein Kinase C-epsilon / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D043884:Receptor, Cannabinoid, CB1; D051744:Protein Kinase C-epsilon