| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
1. Cell volume regulation is essential for various fundamental cell functions including cell cycle progression, apoptosis and migration. It has been suggested that K^+ channels, Cl- channels, water channels, Na^+/H^+ exchangers, and TRP channels are involved in cell volume regulation. RT-PCR analysis was performed to examine the expression of ClC channels and aquaporins in Jurkat cells and human T cells. ClC-3A, ClC-3B and ClC-5 were expressed in Jurkat cells and human T cells, and ClC-4 was expressed in human T cells. AQP3 was expressed in Jurkat cells and human T cells, and AQP1 and AQP8 were expressed in human T cells. The expression of TRP channels and Na^+/H^+ exchangers was also examined in Jurkat cells. TRPC1, TRPC3, TRPC4 and NHE-1 were expressed in Jurkat cells. 2. Jurkat cell lines overexpressing ClC-3A (Jurkat-3A), ClC-3B (Jurkat-3B) and AQP1 (Jurkat-AQP1), respectively, were established. When the cells were exposed to 40% hypotonic solution, the rate of the regulatory volume decrease was accelerated in all these cell lines in comparison with control cells. 3. In Jurkat-3B but not in Jurkat-3A, the rate of proliferation was accelerated. 4. The activation-induced cell death of Jurkat cells was not affected by overexpressing ClC-3 channels. 5. Cell migration was increased in Jurkat-3B in modified Boyden chamber assay. 6. These results suggest that ClC-3A, ClC-3B, AQP1 and AQP3 are involved in cell volume regulation in T cells, and implicate important and unique roles of ClC-3B in Jurkat cell proliferation and migration. Further analysis on protein-protein interactions involving these channels and transporters will provide an important clue to better understand the molecular basis of cell volume regulation.
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