Akademik Veri Yönetim Sistemi
International conference on Trace elements and minerals 2022, Aachen, Almanya, 5 - 10 Haziran 2022
It has been demonstrated that cytosolic
free Zn2+-level in mammalian cardiomyocytes is less than 1-nM under
physiological conditions and increases markedly under pathophysiological
conditions such as hyperglycemia, hyperinsulinemia, or both. Previously we have demonstrated that an increase in the
[Zn2+]i is closely
associated with significant alterations in excitability and ionic-conductances
of the cardiomyocytes while their exact mechanisms are not clarified yet. In this regard, previously, our experimental data had
implied that [Zn2+]i can increase rapidly
in cardiomyocytes due to Zn2+ release from intracellular stores, at
most, through alterations in both expression and activation and/or inhibition
of to Zn2+-transporters, responsible of Zn2+-efflux from
cytosol under hyperglycemic and hyperinsulinemic conditions. In this context,
we have shown that ZnT7 expression level is decreased in hyperglycemic and
hyperinsulinemic adult rat cardiomyocytes as well as in insulin-resistant
senescent rat cardiomyocytes while ZnT8 expression level is increased in these
samples. Furthermore, we determined significant increases in [Zn2+]i in these cardiomyocytes, besides our confocal analysis have shown their
both sarcoplasmic reticulum and mitochondria localizations. Therefore,
in the present study, we aimed to examine the contributions of the altered
expression levels of these Zn2+-transporters to the increases in [Zn2+]i with pathological
stimuli such as hyperglycemia or hyperinsulinemia. We overexpressed either
ZnT7 or silenced ZnT8 in cultured ventricular cardiomyocytes (H9c2) and examined
their roles in [Zn2+]i,
cytosolic ROS level and mitochondrial membrane potentials in either hyperglycemic
or hyperinsulinemic cells. Over-expression of ZnT7 seems to be
closely related with increases in [Zn2+]i
of cardiomyocytes similar to ones in either hyperglycemia or hyperinsulinemia.
These results are also parallel to the depolarization of mitochondrial membrane
potentials and increases in ROS production. Interestingly, silencing of ZnT8
could slightly but significantly decrease high [Zn2+]i in hyperglycemic cells
with a significant increase in [Zn2+]i
normal cells without any significant effect on high ROS production. These
findings imply that under the above pathological stimuli, decrease the expression
level of ZnT7 can be responsible for increases in [Zn2+]i and alterations in
mitochondrial function in cardiomyocytes whereas the increase in the expression
level of ZnT8 can be responsible for maintenance of [Zn2+]i with an effect of
hyperpolarization of mitochondrial membrane potential. Overall, our data confirmed that any change in these
transporters under pathological conditions such as diabetes with or without
insulin resistance can lead to alterations in the redox-state of cardiomyocytes
(Supported through Tübitak SBAG-216S979).