| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
(1) Flow cytometric analysis of Jurkat cells treated with butyric acid revealed that the cells were blocked at the G1/S interface of the cell cycle in dose-dependent fashion. Especially, 21 h treatment with 2.5 mM butyric acid caused the G1 phase arrest. These results suggest that butyric acid blocks transition of the cells from G1 to the S phase of cell cycle and the thereby irreversibly halts the progression of Jurkat cells to mitosis.
(2) We analyzed the effect of butyric acid on cell cycle progression in Jurkat cells by WB analysis. High dose of butyric acid depressed the expression of Cyclin D3 which works in the beginning of G1 phase. However, there was no change in Cyclin D1, D2, Cdk4, and Cdk6 expression. Whereas, butyric acid depressed the expressions of Cyclin A and E which activate in transition from G1 to S phase. Butyric acid also depressed Cdk 2 expression which is Cyclin A- and E-dependent kinase. High dose of butyric acid increased the expression of p21〜<CIP1/WAF1> which
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is inhibitor of Cyclin-Cdk complex. Butyric acid also depressed the expressions of Cyclin A and E which activate in transition from G2 to M phase, however, did not effect Cdc 2 expression which is Cyclin A- and E-dependent kinase.
(3) To examine the transcriptional pathways activated downstream of butyric acid-sensitization, cDNA microarrays were used to monitor transcriptional changes in Jurkat cells upon treatment with butyric acid. Butyric acid treatment primarily resulted in increased expression of proapoptotic genes such as Bax, Bad, Bak, Caspase-3, -6, -7, -8, -9, while the expression of anti-apoptotic mediators such as Bcl-2 and glutatione was decreased. A repression of ERK and an induction of JNK were also observed. Thus, the expression profile of butyric acid-treated Jurkat cells was confirmed by means of cDNA array.
These results suggest that butyric acid-incudec T cell apoptosis s involved in cell cycle arrest through the increase of p21〜<CIP1/WAF1> expression followed by the decrease of Cdk2-Cyclin E and Cdk2-Cyclin A. Less
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