title: Dexmedetomidine protects against apoptosis induced by hypoxia/reoxygenation through the inhibition of gap junctions in NRK-52E cells.
abstract: OBJECTIVE
  The α2-adrenoceptor inducer dexmedetomidine (Dex) provides renoprotection against ischemia/reperfusion (I/R) injury, but the mechanism of this effect is largely unknown. The present study investigated the effect of Dex on apoptosis induced by hypoxia/reoxygenation (H/R) and the relationship between this effect and gap junction intercellular communication (GJIC).
  
  
  METHODS
  In vitro, two cell lines of normal rat kidney proximal tubular cells (NRK-52E) and HeLa cells that were transfected with a connexin 32 (Cx32) plasmid were exposed to H/R. The role of Dex in the modulation of H/R-induced apoptosis was explored by the manipulation of connexin expression, and hence gap junction (GJ) function, using a GJIC inhibitor, heptanol, and a GJIC inducer, retinoic acid. GJ function and the Cx32 protein level were determined by the parachute dye-coupling assay and Western blotting, respectively.
  
  
  RESULTS
  Dex and heptanol significantly reduced H/R-induced apoptosis in NRK-52E cells. The anti-apoptosis effect of Dex was exhibited only in Cx32-expressing HeLa cells. One hour Dex exposure inhibited GJ function mainly via a decrease in Cx32 protein levels in NRK-52E cells.
  
  
  CONCLUSIONS
  Our data suggest that Dex reduced H/R-induced apoptosis through the inhibition of GJ activity by reducing Cx32 protein levels.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Chenfang
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China. Electronic address: heiziqing@sina.com.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020927:Dexmedetomidine / Q000494:pharmacology*; D005434:Flow Cytometry; D017629:Gap Junctions / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D020011:Protective Agents; D020927:Dexmedetomidine; D010100:Oxygen
keywords: Apoptosis; Dexmedetomidine; Gap junction intercellular communication; HeLa cell; Hypoxia/reoxygenation; NRK-52E cell