Billur 2016 Biol Trace Elem Res
| Billur D, Tuncay E, Okatan EN, Olgar Y, Durak AT, Degirmenci S, Can B, Turan B (2016) Interplay between cytosolic free Zn2+ and mitochondrion morphological changes in rat ventricular cardiomyocytes. Biol Trace Elem Res 174:177-188. |
Billur D, Tuncay E, Okatan EN, Olgar Y, Durak AT, Degirmenci S, Can B, Turan B (2016) Biol Trace Elem Res
Abstract: The Zn2+ in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO4 (extracellular exposure) or Zn2+ pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn2+ exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in ZnPO4- or ZnPT-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn2+-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during 1-ΞΌM ZnPT minute applications by using confocal microscopy. We also showed that 1-ΞΌM ZnPT incubation induced significant increases in the phosphorylation levels of GSK3Ξ² (Ser21 and Ser9), Akt (Ser473), and NFΞΊB (Ser276 and Thr254) together with increased expression levels in ER stress proteins such as GRP78 and calregulin. Furthermore, a new key player at ER-mitochondria sites, promyelocytic leukemia protein (PML) level, was markedly increased in ZnPT-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn2+ can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in ER-mitochondria cross talk.
Labels:
Organism: Rat
Tissue;cell: Heart
