2002 Fiscal Year Final Research Report Summary
Molecular biological study of cytotoxicity due to leukotoxins and their metabolites
| Project/Area Number |
12470135
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Fukui Medical University |
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Principal Investigator |
ISHIZAKI Takeshi Fukui Medical University Faculty of Medicine Professor, 医学部, 教授 (80151364)
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| Co-Investigator(Kenkyū-buntansha) |
AMESHIMA Shingo Fukui Medical University University Hospital Associate Professor, 医学部附属病院, 講師 (60262614)
MATSUKAWA Shigeru Fukui Medical University Faculty of Medicine Assistant Professor, 医学部, 助教授 (00092809)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Leukotoxin / Epoxide / Linoleate / Cell-cycle / Cyclin-dependent kinase |
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| Research Abstract |
We continued to study the effect of Leukotoxin (Lx), a linoleate epoxide, on the cell cycle. By using cultured human pulmonary arterial cells (HPEAC), we assessed the effect of antisense p16 INK4aS-oligo in terms of cell growth and used senescence-associated(SA)- β galactosidase staying for evaluating the degree of cell senescence in the presence/absence of Lx.
Results : 1) Cell cycle of the HPEAC was arrested at the phase of G1 in the presence of Lx. The capability of DNA synthesis recovered when Lx was excluded or when pretreated with antisense p16INK4aS-oligo. The expression of mRNA and protein of p16INK4a was increased 3-fold at 48hr after addition of Lx and 4-fold at 96hr, respectively. However, either antisense p16 INK4aS-oligo or washout of Lx suppressed such an effect of Lx.
2) When HPEAC passed PD50 the capability of growth of HPEAC was loosed and positive stained cells with SA-β galactosidase were increased. Whereas Lx suppressed the increase of SA-β galactosidase cells. The simultaneous presence of Lx and antisense p16INK4aS-oligo raised the cell number of positive SA-β galactosidase stain.
Our current experiment suggests that Lx caused cell growth suppression and furthermore cell senescence suppression.
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