2005 Fiscal Year Final Research Report Summary
The elucidation of the apoptosis inhibitory action of SMP30.
| Project/Area Number |
15603010
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
細胞死(アポトーシス)
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| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
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Principal Investigator |
HANDA Setsuko Tokyo Metropolitan Foundation for Research on Aging And Promotion of Human Welfare, Research assistant, 東京都老人総合研究所, 助手 (30360697)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Naoki Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Vice director, 東京都老人総合研究所, 副所長 (00115940)
ISHIGAMI Akihiko Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research scientist, 東京都老人総合研究所, 主任研究員 (50270658)
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| Project Period (FY) |
2003 – 2005
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| Keywords | apoptosis / SMP30 / aging / liver / Akt / knockout mice / vitamin C / gluconolactonase |
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| Research Abstract |
Senescence marker protein-30 (SMP30) is a 34-kDa protein whose tissue levels in the liver, kidney, and lung decrease with aging. To elucidate the physiological role of this protein, we introduced a null mutation of the SMP30 gene into the germ line of mice, and then investigated the tissue susceptibility for apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) using primary cultured hepatocytes. Consequently, cells that are completely lacking SMP30 (SMP30-/-) were more susceptible to apoptosis induced by TNF-alpha plus actinomycin D (Act-D) than SMP30+/+ hepatocytes, indicating that SMP30 can protect cells from apoptosis induced by TNF-alpha plus Act-D. However, the responsible mechanism(s) for anti-apoptotic effect of SMP30 has not been fully understood. Therefore we aimed in this study that the elucidation of the apoptosis inhibitory action of SMP30.
Human hepatocellular carcinoma cell line was transfected with pcDNA3/SMP30 (SMP30 transfectants), or as a control with pcDNA3 (mock transfectants). When cells were exposed to 20 ng/ml tumor necrosis factor-alpha (TNF-alpha) plus 10 ng/ml actinomycin D (Act-D) for 15 h, the viability of cells was decreased in both SMP30 and mock transfectants. However, the viability of cells was threefold higher in SMP30 transfectants than mock transfectants. Cell death was confirmed as apoptosis by TUNEL assay. The presence of trifluoperazine, a calmodulin (CaM) inhibitor, attenuated anti-apoptotic effect of SMP30 in both transfectants, but the effect was more prominent in SMP30 transfectants. Western blot analyses revealed that Akt, which acts as a survival factor in cells, was activated in SMP30, but not mock, transfectants either in the presence or absence of TNF-alpha plus Act-D. Further, trifluoperazine inhibited Akt activation in SMP30 transfectants. We therefore propose that interplay between CaM and SMP30 regulates Akt activity, and thus SMP30 acts as a survival factor in hepatocytes.
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[Journal Article] Senescence Marker Protein-30 (SMP30) induces formation of microvilli and bile canaliculi in Hep G2 cells.2005
Author(s)
Ishigami, A., Fujita, T., Inoue, H., Handa, S., Kubo, S., Kondo, Y., Maruyama, N.
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Journal Title
Cell & Tissue Res. 320
Pages: 243-249
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Immunohistochemical localization of senescence marker protein-30 (SMP30) in the submandibular gland and ultrastructural changes of the granular duct cells in SMP30 knockout mice.2005
Author(s)
Ishii, K., Tsubaki, T., Fujita, K., Ishigami, A., Maruyama, N., Akita, M.
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Journal Title
Histol.Histopathol. 20
Pages: 761-768
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The increased protein oxidation and the altered expression of Ca2+ regulatory proteins in senescence marker protein 30 deficient brain.
Author(s)
Son, T.G., Zou, Y., Jung, K.J., Je, J.H., Yu, B.P., Ishigami, A., Maruyama, N., Lee, J.
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Journal Title
Mech.Aging Dev. (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Accelerated tubular cell senescence in SMP30 knockout mice.
Author(s)
Yumura, W, Imasawa, T., Suganuma, S., Ishigami, A., Handa, S., Kubo, S., Maruyama, N.
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Journal Title
Histol.Histopathol. (in press)
Description
「研究成果報告書概要(欧文)」より
