Next, we overexpressed wild-type ATP13A2 in ATP13A2−/− cells and treated ZnCl2 to test whether restoration of ATP13A2 expression reverses Zn2+ cytotoxicity. ATP production rate was determined following the previously described protocol (47). These findings confirm the involvement of ROS in Zn2+-mediated cytotoxicity in ATP13A2−/− cells and also suggest that a loss of ATP13A2 results in altered ROS metabolism, which contributes to an increased susceptibility to Zn2+ and induction of protective changes in the cellular antioxidant system.
NIH
Parkinson's disease patient information compiled by the National Institute of Neurological Disorders and Stroke (NINDS). As Zn2+ has been shown to increase mitochondrial ROS production (34), we then examined whether ROS was involved in the observed Zn2+-induced cytotoxicity. Mitochondrial function and ROS production were assessed in hONs cells exposed to ZnCl2. 2018 Mar 6 [Epub ahead of print]. Promotion of mitochondrial fusion using IBMX treatment, prevented ZnCl2-mediated mitochondrial fragmentation in ATP13A2−/− cells and further increased mitochondrial interconnectivity in the control. Smell disturbances. Furthermore, we observed an oxidant-induced increase in [Zn2+]i resulting in mitochondrial depolarization in ATP13A2−/− cells, which was effectively prevented by Zn2+ chelation with TPEN (Fig.
The failure to detect a difference in mitochondrial O2− production (data not shown) may alternatively be due to a short half-life of O2− or the subtle difference in O2− levels induced by ZnCl2 treatment.
4C), negating the possibility of random detection of the decreased co-localization in the ATP13A2−/− cells. © The Author 2014. 1993 Nov;43(11):2262-8 Methods: NS, not significant; #P < 0.05 by Mann–Whitney U test.
Increased sensitivity to the exogenous application of ZnCl2 and H2O2 (both of which increase [Zn2+]i by direct uptake into cells for ZnCl2 and oxidant-induced release from zinc-binding proteins for H2O2), together with the protective effects of antioxidant treatment (NAC) and Zn2+ chelation (TPEN), underpin the pathophysiology of Zn2+ toxicity in ATP13A2-deficient cells (Fig. Values in the graphs are represented as mean ± SD.
The demographics of our patient groups were similar to those reported by other investigators, making age, sex and nutritional status unlikely explanations for our findings. When treated with ZnCl2, ATP13A2−/− cells showed a dose-dependent and significant decrease in cell viability (P < 0.01), whereas the control cells demonstrated cytotoxicity only at the highest dose tested (P < 0.01, Fig. PD usually affects people around the age of 70 years but can occur earlier.
In addition, IBMX treatment reversed the Zn2+-induced reduction in cell viability for ATP13A2−/− cells (P < 0.05, Fig. Investigators led by Chadwick W. Christine, MD, a neurologist at the University of California, San Francisco, sought to understand what contributes to variation in the progression of Parkinson’s disease. Receive news and offers from our other brands? hONs cells were seeded in a black 96-well plate at 1 × 104 cells per well and grown for 24 h. For assessment of ΔΨm, the cells were incubated with either dimethyl sulfoxide (DMSO) or 25 µm CCCP for 4 h in serum-free media. All datasets were tested for normality using the Shapiro–Wilk test and analysed for statistical significance using SPSS (version 21, IBM, Armonk, NY, USA). Among the genes investigated, 19 (8 ZnTs and 11 ZIPs) were expressed in the hONs cells, while the expression of ZnT2, ZIP5, ZIP8 and ZIP12 was not detected with the PCR conditions employed (see Materials and Methods).