Xiao-hui Zhao1, Yi-zhi Peng, Yuan-yuan Wang, Yue-sheng Huang. 1. Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, the Third Military Medical University, Chongqing, P. R. China.
Abstract
OBJECTIVE: To explore the effect of endogenous heat shock protein 90 (HSP90) on the AKT signaling pathway of hypoxic cardiomyocytes. METHODS: The hypoxia model of neonatal rat cardiomyocyte was established. The cells were randomly divided into normal control, hypoxia, Geldanamycin (GA, with hypoxia after Geldanamycin treatment) groups. The myocardial cell activity and the expression of endogenous HSP90 and AKT were determined with MTT and Western blotting, respectively at 1, 3, 6, 12, 24 and 48 post-hypoxia hours (PHH). The apoptotic index (AI) of cardiomyocytes were determined with TUNEL method at 24 PHH. RESULTS: (1) At 24 and 48 PHH, the activity of cardiomyocytes in hypoxia group and GA group were evidently lower than that in control group (P < 0.05). The activity of cardiomyocyte in GA group began to decrease at 12 PHH, and it was obviously lower than that in hypoxia group at 48 PHH (P < 0.05). (2) At 24 PHH, the AI in hypoxia group (10.7 +/- 1.2)% was obviously higher than that in normal control group [(1.9 +/- 0.3)%, P < 0.05], while it was obviously lower than that in GA group [(26.3 +/- 5.3)%, P < 0.01]. (3) The expression of endogenous HSP90 and AKT in hypoxia and GA groups were markedly increased compared with that of normal controls at 12 PHH, and it decreased at 24 PHH in hypoxia and GA groups, especially in the latter. CONCLUSION: Endogenous HSP90 plays important roles in maintaining the cardiomyocyte activity, and its level might affect the expression of AKT.
OBJECTIVE: To explore the effect of endogenous heat shock protein 90 (HSP90) on the AKT signaling pathway of hypoxic cardiomyocytes. METHODS: The hypoxia model of neonatal rat cardiomyocyte was established. The cells were randomly divided into normal control, hypoxia, Geldanamycin (GA, with hypoxia after Geldanamycin treatment) groups. The myocardial cell activity and the expression of endogenous HSP90 and AKT were determined with MTT and Western blotting, respectively at 1, 3, 6, 12, 24 and 48 post-hypoxia hours (PHH). The apoptotic index (AI) of cardiomyocytes were determined with TUNEL method at 24 PHH. RESULTS: (1) At 24 and 48 PHH, the activity of cardiomyocytes in hypoxia group and GA group were evidently lower than that in control group (P < 0.05). The activity of cardiomyocyte in GA group began to decrease at 12 PHH, and it was obviously lower than that in hypoxia group at 48 PHH (P < 0.05). (2) At 24 PHH, the AI in hypoxia group (10.7 +/- 1.2)% was obviously higher than that in normal control group [(1.9 +/- 0.3)%, P < 0.05], while it was obviously lower than that in GA group [(26.3 +/- 5.3)%, P < 0.01]. (3) The expression of endogenous HSP90 and AKT in hypoxia and GA groups were markedly increased compared with that of normal controls at 12 PHH, and it decreased at 24 PHH in hypoxia and GA groups, especially in the latter. CONCLUSION: Endogenous HSP90 plays important roles in maintaining the cardiomyocyte activity, and its level might affect the expression of AKT.
Authors: Mark J Ranek; Marisa J Stachowski; Jonathan A Kirk; Monte S Willis Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-01-19 Impact factor: 6.237