| Project/Area Number |
12470064
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bacteriology (including Mycology)
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY |
|---|
Principal Investigator |
SUGAI Motoyuki Faculty of Dentistry, HIROSHIMA UNIVERSITY, Professor, 歯学部, 教授 (10201568)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHARA Masaru Faculty of Dentistry, HIROSHIMA UNIVERSITY, Research Assistant, 歯学部, 助手 (80253095)
FUJIWARA Tamaki Faculty of Dentistry, HIROSHIMA UNIVERSITY, Research Assistant, 歯学部, 助手 (90274092)
KOMATSUZAWA Hitoshi Faculty of Dentistry, HIROSHIMA UNIVERSITY, Associate Professor, 歯学部, 助教授 (90253088)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
|
|---|
| Keywords | Cytolethal distending toxin / ctinibacillus actinomycetemcomitams / CDTABC complex / lipoptrotein / apoptosis / 細胞膨化致死毒素 / G2 / Mブロック / Actinobacillus actinomycetemcomitans / CDT / cell cycle / 毒素 / 歯周病 / 細胞周期 |
|---|
| Research Abstract |
CDT from Actinobacillus actinomycetemcomitans (A.a) is composed of CDTA, B, and C encoded as cdtA, cdtB and cdtC genes tandemly-located on the chromosomal cdt locus. Immunoprecipitation study indicates that CDT forms complex. N-terminal sequencing of purified CDT revealed that 36-43 amino acids of CDTA are further processed at N-terminus probably after lipidmodification of CDTA. Sucrose density gradient ultracentrifuge showed the localization of CDT complex at the outer membrane. Taken together, we propose the hypothetical pathway of CDT secretion from periplasmic space to culture supernatant.
CDT-induced death in T cell lines was accompanied with the biochemical features of apoptosis including membrane conformational change, intranucleosomal DNA cleavage, and increase of caspase activity in the cells. Inhibitors for caspase-2 and -7 showed significant inhibitory effect on CDT-induced apoptosis of Jurkat cells suggesting that CDT possesses an ability to induce human T cell apoptosis through activation of caspase-2 and -7.
Among 45 A.a clinical isolates, CDT activity was found in cell lysate and culture supernatant of all tested strains, but the titer of the toxin in culture supernatant considerably varied among strains. PCR experiments indicated the presence of Y4-type cdt sequences in forty strains, suggesting that CDT production is prevalent in A.a strains.
|
