Chronic exposure to high levels of arsenic is closely associated with nervous system disorders that harm learning, memory, and intelligence. Studies have shown that the primary characteristic of brain damage is neuronal apoptosis. Arsenic induces apoptosis in a variety of nerve cells. Therefore, substance that inhibit apoptosis promise to mitigate arsenic toxicity. Pigment epithelium-derived factor (PEDF) is widely distributed in brain tissues and has various effects on neurons, including induction of apoptosis. Our previous study suggested that PEDF might augment arsenic-induced apoptosis in rat brains. In this study of 151 adults with normal, mild, moderate, and high exposure to arsenic, the measured serum PEDF levels were 15.46 ± 5.87 ng/mL, 17.33 ± 8.22 ng/mL, 19.43 ± 9.51 ng/mL and 21.65 ± 14.46 ng/mL, respectively. Multiple linear regression analysis revealed an independent positive correlation between serum PEDF levels and arsenic exposure in drinking water. To study the underlying mechanism of arsenic-induced apoptosis, we exposed PEDF-transfected PC12 cells to NaAsO2. We discovered that NaAsO2--induced mitochondrial apoptosis was enhanced in cells that over expressed PEDF. Moreover, p53 up regulated modulator of apoptosis (PUMA) gene and B-cell lymphoma 2 (Bcl-2) protein were primary factors in the progression of arsenic-induced apoptosis. Taken together, our results suggest that PEDF inhibition might mitigate arsenic toxicity to nerve cells.
Keywords: Arsenic exposure; Arsenic toxicity; Inhibition of pigment epithelium-derived factor; Nerve cell; Neuronal mitochondrial apoptosis; PC12 cell line.
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