title: Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia.
abstract: BACKGROUND
  The antioxidant mechanism of sevoflurane post-conditioning-induced neuroprotection remains unclear. We determined whether sevoflurane post-conditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defence genes) and haemoxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 activation, in a rat model of transient global cerebral ischaemia/reperfusion (I/R) injury.
  
  
  METHODS
  Eighty-six rats were assigned to five groups: sham (n=6), control (n=20), sevoflurane post-conditioning (two cycles with 2 vol% sevoflurane inhalation for 10 min, n=20), chelerythrine (a PKC inhibitor; 5 mg kg(-1) i.v. administration, n=20), and sevoflurane post-conditioning plus chelerythrine (n=20). The levels of nuclear Nrf2 and cytoplasmic HO-1 were assessed 1 or 7 days after ischaemia (n=10 each, apart from the sham group, n=3).
  
  
  RESULTS
  On day 1 but not day 7 post-ischaemia, Nrf2 and HO-1 expression were significantly higher in the sevoflurane post-conditioning group than in the control group. Chelerythrine administration reduced the elevated Nrf2 and HO-1 expression induced by sevoflurane post-conditioning.
  
  
  CONCLUSIONS
  Sevoflurane post-conditioning increased Nrf2/HO-1 expression via PKC signalling in the early phase after transient global cerebral I/R injury, suggesting that activation of antioxidant enzymes may be responsible for sevoflurane post-conditioning-induced neuroprotection in the early phase after cerebral I/R injury.
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Park
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Y T
authors.initials: YT
authors.lastname: Jeon
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: J W
authors.initials: JW
authors.lastname: Hwang
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea hppark@snu.ac.kr.
authors.forename: H P
authors.initials: HP
authors.lastname: Park
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D003213:Conditioning, Psychological / Q000187:drug effects; D003593:Cytoplasm / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008738:Methyl Ethers / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D000077149:Sevoflurane; D051547:Heme Oxygenase-1; D011493:Protein Kinase C; D053148:Caspase 3
keywords: GA-binding protein transcription factor; anaesthetics, inhalation; haeme oxygenase-1; protein kinase C