Mechanism of cadmium induced apoptosis in the immunocyte.
Cadmium is the major component of polluted environment which can be fatal by mechanisms that are not fully clear. Our study indicates immunosupression may be one of the reason for that. It is well known that cadmium (Cd) has toxic and carcinogenic effects in rhondents and humans, but the effects of cadmium on apoptosis are still not clear. Although some studies have shown that cadmium has apoptotic potential, other studies have shown that cadmium can be anti-apoptotic. In the present study, we aimed to determine the mode of cell death and its mechanism in Swiss albino mice splenocyte by cadmium for its toxic effects. To identify the nature of cell death, our result signifies apoptotic mode of killing. In search of the mechanism behind it we found that cadmium increased cell death and lowered the survival of the host in a dose dependent manner. In search of the reason we found increased expression of the pro-apoptotic proteins p53 in splenic lymphocytes. Here we showed that cadmium induced p53-dependent apoptosis through cooperation between Bcl-xl down regulation without changing the Bcl-2 and Bax expression, the common target of p53. The down regulation of Bcl-xl strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in cadmium induced toxic environment in the host.
Chatterjee
Soumya
S
Department of Environmental Science, University of Kalyani, West Bengal 741235, India.
Kundu
Subhadip
S
Bhattacharyya
Arindam
A
D000818:Animals; D017209:Apoptosis; D002104:Cadmium / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D002467:Cell Nucleus / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D004785:Environmental Pollutants; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D002104:Cadmium; D045304:Cytochromes c; D004247:DNA; D053148:Caspase 3