Akademik Veri Yönetim Sistemi
MOLECULAR AND CELLULAR BIOCHEMISTRY, cilt.440, sa.1-2, ss.209-219, 2018 (SCI-Expanded)
Clinical and experimental studies have shown an association between intracellular free Zn2+ ([Zn2+](i))-dyshomeostasis and cardiac dysfunction besides [Ca2+](i)-dyshomeostasis. Since [Zn2+](i)-homeostasis is regulated through Zn2+-transporters depending on their subcellular distributions, one can hypothesize that any imbalance in Zn2+-homeostasis via alteration in Zn2+-transporters may be associated with the induction of ER stress and apoptosis in hypertrophic heart. We used a transverse aortic constriction (TAC) model to induce hypertrophy in young male rat heart. We confirmed the development of hypertrophy with a high ratio of heart to body weight and cardiomyocyte capacitance. The expression levels of ER stress markers GRP78, CHOP/Gadd153, and calnexin are significantly high in TAC-group in comparison to those of controls (SHAM-group). Additionally, we detected high expression levels of apoptotic status marker proteins such as the serine kinase GSK-3 beta, Bax-to-Bcl-2 ratio, and PUMA in TAC-group in comparison to SHAM-group. The ratios of phospho-Akt to Akt and phospho-NF kappa B to the NF kappa B are significantly higher in TAC-group than in SHAM-group. Furthermore, we observed markedly increased phospho-PKC alpha and PKC alpha levels in TAC-group. We, also for the first time, determined significantly increased ZIP7, ZIP14, and ZnT8 expressions along with decreased ZIP8 and ZnT7 levels in the heart tissue from TAC-group in comparison to SHAM-group. Furthermore, a roughly calculated total expression level of ZIPs responsible for Zn2+-influx into the cytosol (increased about twofold) can be also responsible for the markedly increased [Zn2+](i) detected in hypertrophic cardiomyocytes. Taking into consideration the role of increased [Zn2+](i) via decreased ER-[Zn2+] in the induction of ER stress in cardiomyocytes, our present data suggest that differential changes in the expression levels of Zn2+-transporters can underlie mechanical dysfunction, in part due to the induction of ER stress and apoptosis in hypertrophic heart via increased [Zn2+](i)- besides [Ca2+](i)-dyshomeostasis.