Mechanism of hepatocytes apoptosis induced by the proapoptosis protein Bid.
OBJECTIVE: To investigate the mechanism of hepatocyte apoptosis induced by the proapoptosis protein Bid. METHODS: Mouse primary hepatocytes were isolated from wild-type and Bid-deficient mice and treated with tumor necrosis factor-alpha (TNF-alpha) or anti-Fas antibody to induce cell apoptosis. Immunofluorescence staining of Bax was performed to recognize Bax translocation and its conformational change. The wild-type mice or wild-type mice transfected with the adenovirus carried DN-FADD (Dominant Negative-Fas Associated Death Domain) and the Bid-deficient mice were injected with anti-Fas antibody 2 h before being killed. Caspase 3 and 8 activities were measured. Bands of Bid cleavage and Bax conformational change were detected by Western blot. RESULTS: Death receptors, including TNF-alpha and anti-Fas antibody, induced hepatocytes apoptosis, Bax translocation and conformational change through activation of Bid, which caused Bax to be inserted into the mitochondrial membrane of hepatocytes. The translocation and insertion of Bax were blocked when Bid was knocked out or blocked, and hepatocyte apoptosis was delayed or inhibited. CONCLUSION: Hepatocyte apoptosis induced by death receptors is regulated by Bid and the translocation and insertion of Bax are also dependent on Bid.[1]References
- Mechanism of hepatocytes apoptosis induced by the proapoptosis protein Bid. Bai, L., Cao, C.P., Mao, G.P. Chinese journal of digestive diseases. (2004) [Pubmed]
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