title: Deletion of the aquaporin-4 gene alters expression and phosphorylation of protective kinases in the mouse heart.
abstract: OBJECTIVE
  Aquaporins are channel-forming proteins highly permeable to water and some small molecular solutes. We have previously shown that aquaporin-4 knockout mice have increased tolerance to ischemia. However, the mechanism of cardioprotection was unclear. The aim of the current study was to investigate the effects of aquaporin-4 deletion on baseline expression and phosphorylation of some cardioprotective protein kinases.
  
  
  METHODS
  Proteins were extracted from hearts of aquaporin-4 knockout mice and littermate wild-type controls and analyzed with Western blot. Samples were taken from young (≤ 6 months of age), and old (≥ 1 year) mice.
  
  
  RESULTS
  Western blots showed three different isoforms of aquaporin-4 in wild types, likely representing M1, M23, and Mz. Total AMP-dependent kinase expression was decreased in aquaporin-4 knockout hearts by 18 ± 13% (p = 0.02), while the expression of Akt kinase, extracellular signal regulated kinase 1/2, protein kinase C-epsilon, mitogen-associated kinase P38 and C-Jun N-terminal kinase was unchanged. The phosphorylation of Akt kinase was reduced in hearts from knockout mice by 41 ± 16% (p = 0.01). No other alterations in phosphorylation were found. These effects were only detected in young mice.
  
  
  CONCLUSIONS
  Deletion of the aquaporin-4 gene decreased AMP-dependent kinase expression and Akt kinase phosphorylation in the heart. These changes may influence energy metabolism and endogenous cardioprotection.
authors.affiliation: Department of Emergency and Intensive Care at the Institute of Clinical Medicine , Norway.
authors.forename: Arkady
authors.initials: A
authors.lastname: Rutkovskiy
authors.forename: Lars Henrik
authors.initials: LH
authors.lastname: Mariero
authors.forename: Jarle
authors.initials: J
authors.lastname: Vaage
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D011494:Protein Kinases
keywords: AMPK; Cardiac aquaporins; RISK pathway; cardioprotection; protein kinase C epsilon; protein kinases