Analysis of the mechanism of apoptosis regulated by phosphorylation in newly established cell lines.
| Project/Area Number |
07671212
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Kagawa Medical University |
|---|
Principal Investigator |
NAGAI Masami Kagawa Medical University Hospital, Assistant Professor, 医学部・附属病院, 講師 (40180450)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | Bcl-2 / apoptosis / cell line / phosphorylation / lymphoma / cell cycle / Fas |
|---|
| Research Abstract |
The Bcl-2 extends cell survival by blocking apoptosis, although the details of its mechanism of action remain unclear. Recently, we have established a human pre-B lymphoid cell line termed OZ from a patient with an aggressive lymphoma. OZ has the t (14 ; 18) (q32 ; q2l) translocation and express large amounts of Bcl-2 compared to CCRF-CEM cells. VP16 (40 ug/ml) caused DNA fragmentation (29% of total DNA) typical for apoptosis at 6 hrs In CCRF-CEM cells but no significant changes in OZ cells until 12 hrs following addition of VPI6. Immunoblot analysis revealed that Bcl-2 in untreated OZ cells contained abundant serine-phosphorylated protein. Coincubation with calphostin C (0.2 ug/ml), a protein kinase C (PKC) inhibitor, increased apoptosis in VP16-treated OZ cells. Simutaneous immunoblot analysis revealed down-regulation of phosphorylated Bcl-2. Apoptosis induced by VP16 in CCRF-CEM cells was inhibited partially by the addition of 0.5uM phorbol 12-myristate 13-acetate (TPA). These observations suggest that Bcl-2 function is partly regulated by phosphorylation/ dephosphorylation mechanisms of the PKC system. Hyperphosphorylation of overexpressed Bcl-2 in tumor cells with t (14 ; 18) tralnslocation may play an important role in lymphoma pathogenesis.
|
Report
(3 results)
Research Products
(5 results)
