Mechanism of cadmium induced apoptosis in human peripheral blood lymphocytes: The role of p53, Fas and Caspase-3

作者：Al Assaf Abdullah H; Alqahtani Ali M; Alshatwi Ali A^*; Syed Naveed A; Shafi Gowhar; Hasan Tarique N

来源：Environmental Toxicology and Pharmacology, 2013, 36(3): 1033-1039.

DOI：10.1016/j.etap.2013.09.006

• Cadmium
• Human lymphocytes
• Toxicity
• Apoptosis
• Pro-apoptotic genes expression

Cadmium (Cd) is a major pollutant of environment. It can be fatal to human. In spite of bulk of research and literatures, the mechanism of a fatality against human is still not understood completely. Toxic and carcinogenic effects of Cd in rodents and humans are well known. However, effects of Cd on induction of apoptosis are still elusive. This study indicates immunosuppression and immunotoxicity due to Cd exposure. Present study was undertaken to determine the mechanism of cell death in vitro in human peripheral blood lymphocytes induced by Cd. Our findings suggest the toxicity due to Cd is attributed to programmed cell death-apoptosis. IC50 was calculated at 21.74 mu M. A significant increase of expression of the pro-apoptotic genep53, Fas and Caspase-3 in human lymphocytes was found. Cd induced p53-dependent apoptosis through cooperation between Bak upregulation without changing the Bcl-2 and Box expression. Data of this study compel to speculate that apoptosis may also be attributed to CD95/Fas complex formation, and p53 direct apoptogenic potential at mitochondria. It was confirmed by the increased expression of Caspase-3. Although, this work does not address all the questions regarding the mechanism of Cd induced apoptosis, but these findings establish an important role of p53 and mitochondrial function during apoptosis in human lymphocyte. Moreover, based upon our findings, the role of Fas in Cd induced apoptosis is also undeniable. Hence further investigations are required to understand the different mechanism involved into apoptosis of lymphocytes due to Cd exposure.

• 出版日期2013-11