KMID : 0371320070730050359
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Journal of the Korean Surgical Society 2007 Volume.73 No. 5 p.359 ~ p.365
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Tacrolimus (FK506) Induced Apoptotic Signal Transduction Pathway
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Jung Mi-Ran
Choi Soo-Jin-Na Chung Sang-Young
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Abstract
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Purpose: This study examined the effects of Tacrolimus (FK506) on the expression of the apoptotic signal transduction proteins of Jurkat human T-lymphocytes.
Methods: The cell viability was examined by a MTT assay, DAPI stain, enzyme activity of caspase family proteins, and western blotting for Bcl-2, Bak, Fas, and Fas-L. The cells were cultured in the presence or absence of FK506. FK506 induced cell death was confirmed to be apoptosis by the observation of nuclear fragmentation.
Results: The viability of Jurkat cells was decreased by the addition of FK506 in a dose- and time- dependent manner. The FK506 induced activation of caspase-3 protease was observed. FK506 didn¡¯t increase the catalytic activity of caspase -6, -8, and -9 proteases of Jurkat cells in a time-dependent manner. The viability was improved when a caspase-3 inhibitor was added. However, the caspase-9 inhibitor did not affect the viability. Bak protein expression was increased, and the Bcl-2 protein was decreased for some time. The expression of Fas and Fas-L were unaffected by FK506.
Conclusion: FK506 induces dose- and time-dependent apoptotic cell death, and enhances the apoptosis of Jurkat cell by increasing the expression of Bak and caspase-3. (J Korean Surg Soc 2007;73:359-3)
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KEYWORD
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Tacrolimus (FK506), Jurkat cell, Apoptosis, Bak protein, Caspase-3
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