Durak 2017 MiP2017
Zinc is an essential trace element in human body via playing important roles in regulation of many physiological processes. The free zinc (Zn2+) has special interest, because it can be easily exchanged between different compartments of the cell and bind to numerous proteins, thereby altering their biological activity. The available literature suggests that the maintenance of Zn2+-homeostasis is achieved generally through two main transport systems such as Zn2+-transporting proteins and Zn2+-buffer system. Zn2+-transporters are located on the plasma membrane as well as on many organelles of mammalian cells including in the nucleus, sarco(endo)plasmic reticulum [S(E)R], Golgi apparatus, and mitochondria. In our previous studies we have shown that reactive oxygen/nitrogen species (ROS/RNS) induced significant increases in the basal level of [Zn2+]i in cardiomyocytes via Zn2+ release from subcellular stores, and thereby, lead to impaired mitochondrial and heart function. Little is known about Zn2+-dependent mitochondrial function or the distribution of Zn2+-transporters on the mitochondrial inner membrane. In this study, we aimed to examine how the level of mitochondrial [Zn2+]i changes in the pathophysiological condition as well as possible contribution of the contribution of Zn2+-transporters. Ventricular cell line, H9c2 cells were treated with doxorubicin to mimic heart failure at the cellular level (adriamycin; 5 µM for 24 h). We first invesitigated the mitochondrial localization of ZIP7 and ZnT7 in cardiomyocytes and in isolated mitochondrial fractions. A markedly decreased protein level of ZIP7 was observed doxorubicin-treated H9c2 cells whilst ZnT7 expression was increased. Additionally, under pathological conditions, a significant increase in mitochondrial [Zn2+] and depolarized mitochondrial membrane potential in doxorubicin-treated H9c2 cells were observed. As conclusion, our data point out the possible contribution of Zn2+-transporters located on mitochondria to redistribution of cellular [Zn2+] and therefore, alltogether their contribution to impaired heart function via altered mitochondrial function.
• Keywords: Zinc, Mitochondria, Cardiomyocytes • Bioblast editor: Kandolf G
Labels: MiParea: mt-Medicine
- Dept Biophysics, Ankara Univ Fac Medicine, Ankara, Turkey. - email@example.com