title: Propofol depresses the cytotoxicity of X-ray irradiation through inhibition of gap junctions.
abstract: BACKGROUND
  General anesthetics (e.g., propofol) influence the therapeutic activity of intraoperative radiotherapy but the mechanism of the effects is largely unknown. It has been reported that propofol inhibits gap junction (GJ) function briefly, and a functional GJ enhances the efficacy of radiotherapy in some cancer cells. Yet the mechanisms underlying the inhibition of GJ function by propofol and the influence of propofol on therapeutic activity of intraoperative radiotherapy are unknown.
  
  
  METHODS
  The role of propofol at clinically relevant concentrations in the modulation of radiograph-induced cytotoxicity in HeLa cells transfected with connexin 32 (Cx32) plasmid was explored by manipulation of connexin expression, GJ presence, and function. GJ function, Cx32 protein level, and Cx32 mRNA expression were determined by "Parachute" dye-coupling assay, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively.
  
  
  RESULTS
  Propofol significantly reduced radiograph-induced cytotoxicity only in the presence of functional GJ. Four-hour propofol exposure inhibited GJ function mainly by diminution of Cx32 protein levels but without influence on Cx32 mRNA expression.
  
  
  CONCLUSIONS
  These results suggest that propofol inhibits the function of the GJ through the reduction of Cx32 protein levels by a transcription-independent mechanism. They further indicate that propofol depresses the cytotoxicity of radiograph irradiation through inhibition of GJ activity.
authors.affiliation: Department of Anaesthesia, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Hong
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D006367:HeLa Cells; D006801:Humans; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D014965:X-Rays; D000097002:Gap Junction beta-1 Protein
chemical_list: D018686:Anesthetics, Intravenous; D017630:Connexins; D015742:Propofol; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein