Excessive zinc chloride induces murine photoreceptor cell death via reactive oxygen species and mitochondrial signaling pathway

Abstract

Zinc (Zn) is a fundamental trace element for cell viability and physiology, and concentrations above the physiological level may lead to cell damage. In order to explore the effect of zinc chloride (ZnCl2) on murine photoreceptor cells, in this study, we investigated the alterations of murine photoreceptor cell proliferation and cell morphology after exposure to various concentrations of ZnCl2, determined the levels of hydrogen peroxide, hydroxyl radicals, cytochrome c, and ATP before and after cells exposure to different concentrations of ZnCl2, monitored the changes of mitochondrial membrane potential, and further explored the expressions of BCL2-associated X (Bax) and B cell CLL/lymphoma (Bcl)-2 at gene and protein levels. The results indicated that appropriate ZnCl2 levels can enhance the cell proliferation, whereas high levels of ZnCl2 could apparently inhibit cell growth, exaggerate the generation of both hydrogen peroxide and hydroxyl radicals, collapse the mitochondrial membrane potential, and accelerate cytochrome c release into cytosol, decrease the ATP production, elevate the Bax production, and reduce the Bcl-2 expression, thereby disrupting the mitochondrial homeostasis. Consequently, the disrupted mitochondrial homeostasis initiates the mitochondria-mediated apoptotic signaling pathway, leading to cell death. Taken together, the results suggest that the over generation of reactive oxygen species and the activated mitochondrial signaling pathway play an important role in ZnCl2-induced murine photoreceptor cell death.