J Korean Surg Soc.  2007 Nov;73(5):359-365.

Tacrolimus (FK506) Induced Apoptotic Signal Transduction Pathway

• Jung MR
• Choi SJ
• Chung SY

Abstract

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.

Keyword

Tacrolimus (FK506); Jurkat cell; Apoptosis; Bak protein; Caspase-3

MeSH Terms

Apoptosis
bcl-2 Homologous Antagonist-Killer Protein
Blotting, Western
Caspase 3
Caspase 9
Cell Death
Cell Survival
Humans
Jurkat Cells
Peptide Hydrolases
Signal Transduction*
T-Lymphocytes
Tacrolimus*
Caspase 3
Caspase 9
Peptide Hydrolases
Tacrolimus
bcl-2 Homologous Antagonist-Killer Protein