Deletion of the aquaporin-4 gene alters expression and phosphorylation of protective kinases in the mouse heart

作者：Rutkovskiy Arkady^*; Mariero Lars Henrik; Vaage Jarle

来源：Scandinavian Journal of Clinical & Laboratory Investigation, 2014, 74(6): 500-505.

DOI：10.3109/00365513.2014.905698

• Cardiac aquaporins
• protein kinases
• RISK pathway
• protein kinase C epsilon
• cardioprotection
• AMPK

Aim. 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. Conclusion. 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.

• 出版日期2014-9