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

Abstract

were found in the hippocampus of As-exposed mice. The expressions of the Bcl-2 gene and its protein in the hippocampus of As-exposed mice were significantly lower than those in the control group (p<0.05). However, the expressions of the Bax gene and its protein, and the expression ratio of Bax/Bcl-2 in the hippocampus were significantly higher in the groups exposed to As than in the control group (p<0.05). Moreover, the activity of caspase-3 in the hippocampus of mice exposed to As was higher than that in the control (p<0.05). Conclusions:These results indicate that subchronic exposure to As induces apoptosis in the hippocampus of mice by disturbing normal Bax/Bcl-2 regulatory pathways. Meanwhile, it is suggested that the induced apoptosis in the hippocampus may be at least partly responsible for As-induced neurotoxicity. (J Occup Health 2015; 57: 212-221) Key words: Apoptosis, Arsenic trioxide, Bax, Bcl-2, Hippocampus, Neurotoxicity Arsenic (As), a naturally occurring toxic metalloid found in both inorganic and organic forms, is ubiquitous in the environment and contaminates water as a result of geological and industrial pollution 1) . Moreover, some kinds of arsenide, such as arsenic trioxide (As 2 O 3 ), are also widely used for the treatment of malignant tumors 2) . In As-contaminated areas, the As concentration in drinking water or groundwater ranges from 0.25 to 2.1 ppm and even reaches >3.0 ppm in some severely contaminated areas 3−5) . Exposure to As has been associated with increasing incidences of various chronic diseases, including peripheral vascular disease, cardiovascular disease, diabetes mellitus, and various cancers 6) . As is also a potent neurotoxicant, and subchronic or chronic As exposure causes severe nervous system Abstract: Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl-2/Bax pathway: Yachen WANG, et al. Department of Occupational and EnvironmentalHealth, Dalian Medical University, P.R. ChinaObjectives: The aim of this study was to identify whether arsenic (As) exposure could induce hippocampal neural apoptosis in vivo. Methods: Sixty-four mice were randomly divided into 4 groups of 16 each. Group 1 orally received drinking water alone as a control. Groups 2−4 were given arsenic trioxide (As 2 O 3 ) orally at the doses of 1 ppm, 2 ppm and 4 ppm, respectively. All the treatments continued for 60 days. Morphological changes in the hippocampus were observed by HE staining. Apoptosis in the hippocampus was examined by TUNEL assay and transmission electron microscopy. The expression levels of Bcl-2 and Bax genes and their proteins in the hippocampus were determined by realtime PCR and Western blotting. The activity of caspase-3 was determined by spectrophotometry. Results: Abnormal histopathological changes and apoptosis

Retracted: Effects of microRNA‐129 and its target gene c‐Fos on proliferation and apoptosis of hippocampal neurons in rats with epilepsy via the MAPK signaling pathway

“…And changes in the expression ratio of Bax to Bcl‐2 might activate caspase‐3‐like protease in hippocampal neurons, leading to cell death (Tamatani, Ogawa, Nunez, & Tohyama, ). Bax and Bcl‐2 are significant members of the Bcl‐2 family, among which Bax could promote apoptosis and Bcl‐2 played an important role in preventing apoptosis (Wang et al, ). Apoptosis is triggered by high expression of Bcl‐2 in normal photoreceptors (Shinoura et al, ).…”

Retracted: Protection of miR‐19b in hypoxia/reoxygenation‐induced injury by targeting PTEN

“…(b,d), The protein expressions of PTEN, p-Akt/Akt, Bcl-2/Bax, and cleaved caspase 3 in PC12 (b) and BV2 (d) cells in different transfection groups detected by western blot analysis; Different letters meant the significant difference, whereas same letters indicated no statistical significance. H/R: hypoxia/reoxygenation; miR: microRNA; NC: negative control; qRT-PCR: quantitative reverse-transcription polymerase chain reaction; si-PTEN: small interfering PTEN from mitochondria into the cytoplasm to induce cascades of cell apoptosis; meanwhile, Bax protein will bind to mitochondria to form mitochondria-Bcl-2 dimers, especially Bax oligomer, which further stimulates the release of cyt-c and eventually activating the expression of caspase 3(Ghosh, Das, Mandal, Dungdung, & Sarkar, 2010;Gogvadze, Robertson, Zhivotovsky, & Orrenius, 2001;Nicholls & Budd, 2000;Y. Wang et al, 2015).…”

Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF‐kB/NLRP3 pathway

“…Proteins belonging to the Bcl‐2 family of proteins are regulators of apoptosis, and Bcl‐2 and Bax are representative proteins of this family. In theory, Bcl‐2 prevents apoptosis, while Bax plays a role in promoting apoptosis . In addition, the ratio of Bax/Bcl‐2 is believed to be a reliable indicator of apoptosis .…”

“…In theory, Bcl-2 prevents apoptosis, while Bax plays a role in promoting apoptosis. 37 In addition, the ratio of Bax/Bcl-2 is believed to be a reliable indicator of apoptosis. 38 Interestingly, a previous study showed that the knockdown of NLRP3 protects cells from apoptosis.…”