Involvement of Fas/FasL system in apoptotic signaling in testicular germ cells of male Wistar rats injected i.v. with microcystins

Donghu Experimental Station of Lake Ecosystems, State Key Laboratory for Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China.
Toxicon (Impact Factor: 2.49). 08/2009; 54(1):1-7. DOI: 10.1016/j.toxicon.2009.01.035
Source: PubMed


Previous studies have shown that gonads were the second target organ of microcystins (MCs), and that MCs exposure exerted obvious toxic effects on male reproductive system of mammals. However, relevant molecular evidences are still lacking. Fas-signaling pathway plays a key role in toxicant-induced germ cell apoptosis. This study was to evaluate the responses of Fas/FasL system related genes and proteins in testes of rats injected intravenously with MCs. Enhanced apoptosis of germ cells in the testes of MCs-treated rats was detected by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) associated with up-regulation of the Fas/FasL system. Both Fas and FasL protein expression were induced evidently from 1 h post-injection, and this high expression level maintained throughout the experiment. In addition, the activation of caspase-8 and caspase-3 protein was also observed, which were indicators of apoptosis. These results suggested the likely involvement of Fas/FasL system in the MCs-induced germ cell apoptosis. It is also suggested that MCs can cause damage to Sertoli cells directly.

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    • "86.7 g MC-LR eq/kg 1, 2, 4, 6, 12, 24 h c-fos ↑, c-jun ↑, c-myc ↑ [56] Male Wistar rats Cyanobacterial crude extracts i.v. 80.5 g MC-LR eq/kg 1, 2, 4, 6, 12, 24 h Apoptosis, induction of Fas/FasL system [57] Male Wistar rats Cyanobacterial crude extracts i.v. 87 g MC-LR eq/kg 1, 2, 4, 6, 12, 24 h p53 ↑, Bax ↑, Bcl-2 "
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    • "A single dose i.v. in rats resulted in an increase in liver sphingolipid, implicating ceramide-mediated apoptosis, a dosedependent decrease in PP2A expression, and a dose-dependent decreased expression of Bcl2 family proteins, involved in cell cycle/apoptosis regulation (Billam et al., 2008). Toxic effect may ultimately depend upon the ability of antioxidant pathways to counteract oxidative damage (Jayaraj et al., 2006, 2007; Xiong et al., 2009). Furthermore, as tumor-promoting compounds, MCs, through dysregulation of phosphorylation, may result in promotion of proto-oncogenes, while MCs also induce DNA damage in hepatocytes along with other cell lines (Zegura et al., 2003, 2008). "
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