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KMID : 0371320070730030191
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Journal of the Korean Surgical Society
2007 Volume.73 No. 3 p.191 ~ p.197
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Cytotoxic Mechanism of FK506 on Human T Lymphocytes
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Kim Kwang-Yong
Kim Gwang-Hyun
Park Chan-Yong
Choi Soo-Jin-Na
Chung Sang-Young
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Abstract
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Purpose: FK506 (Tacrolimus) has been widely used as an immunosuppressant. We examined the effects of FK506 on the activation, proliferation and expression of cytotoxic effector molecules of Jurkat human T-lymphocytes.
Methods: We investigated the effects of this compound on cell viability, the production of reactive oxygen species and mitochondrial dysfunction. The cells were cultured in the presence or absence of FK506. Flow cytometric analysis was performed after staining with PI. The viability of the Jurkat cells was decreased by the addition of FK506 in a dose-and time-dependent manners.
Results: FK506-induced cytotoxicity was characterized by G0/G1 phase cell-cycle arrest. FK506 induced cell death was confirmed by the caspase-3 protease activation. In addition, the pharmacologic scavenging study of reactive oxygen species (ROS), including H2O2, revealed that cytotoxicity was achieved by the generation of ROS, which might modulate the mitochondrial dysfunction.
Conclusion: These results suggest that FK506 functions in CDK4-cyclin D1 mediated cell-cycle arrest of Jurkat cells via generation of ROS and mitochondrial dysfunction.
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KEYWORD
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FK 506, Tacrolimus, Human T lymphocyte, Jurkat cell, Immunosuppressant, Cytotoxic mechanism
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