Role of Pigment Epithelium-Derived Factor (PEDF) in Arsenic-Induced Cell Apoptosis of Liver and Brain in a Rat Model

Abstract

Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.

Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl‐2/Bax pathway

“…Because Bcl-2 homodimerizes with itself and forms heterodimers with Bax and Bax is functionally neutralized by heterodimerization with Bcl-2, the ratio of Bcl/Bax protein could ultimately tip the balance toward cell survival or cell death 38) . Zhang et al (2013b) reported that the ratio of Bax/Bcl-2 in the liver and brain following exposure to As was significantly increased compared with that of their control group 18) . In the present study, subchronic exposure to As also increased the ratio of Bax/Bcl-2 expression in the hippocampus of mice, which is consistent with the results reported by Zhang et al (2013b) 18) .…”

“…Zhang et al (2013b) reported that the ratio of Bax/Bcl-2 in the liver and brain following exposure to As was significantly increased compared with that of their control group 18) . In the present study, subchronic exposure to As also increased the ratio of Bax/Bcl-2 expression in the hippocampus of mice, which is consistent with the results reported by Zhang et al (2013b) 18) . This indicates that subchronic exposure to As disturbed expression of the Bcl-2 family proteins in the hippocampus of mice.…”

“…Pachauri et al (2013) showed that chronic As exposure induced neuronal apoptosis in the guinea pig brain 17) . Zhang et al (2013b) reported that apoptosis was induced by chronic exposure to 50 mg/l As in the brain of rats 18) . Furthermore, there was a close relationship between the level of As exposure and the proportion of apoptotic cells.…”

“…Proteins of the Bcl-2 family are regulatory molecules of apoptosis, and Bax and Bcl-2 are representative members of this family 23) . The Bax promotes apoptosis, while the Bcl-2 plays a role in preventing apoptosis 18) . A large body of evidence has demonstrated that As 2 O 3 -induced apoptosis in tumor cells has been associated with the downregulation of Bcl-2 and the upregulation of Bax 35,36) .…”

Role of PTEN-Akt-CREB Signaling Pathway in Nervous System impairment of Rats with Chronic Arsenite Exposure

“…NaAsO 2 was administered in drinking water at concentrations of 0, 5, 10, and 50 mg/L. The dose of NaAsO 2 was determined on the basis of LD 50 values in the rats [21]. During the whole experimental period, animals had free access to food and water.…”