Molecular mechanism for aging control
Project/Area Number |
20390085
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General medical chemistry
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Research Institution | Juntendo University |
Principal Investigator |
SHIRASAWA Takuji Juntendo University, 大学院・医学研究科, 客員教授 (80226323)
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Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Takahiko 地方独立法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究員 (40301791)
TOMITA Kengo 慶応義塾大学, 医学部, 助教 (50317129)
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Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
|
Keywords | 加齢 / 酸化ストレス / 脂肪肝 / NASH / モデルマウス / SOD / 肥満 / レプチン |
Research Abstract |
To investigate pathological role of oxidative stress on nonalcoholic steatohepatitis (NASH), we used CuZn-SOD-deficient mice, which developed spontaneous fatty liver with increased oxidative stress. Although methionine and choline-deficient (MCD) diet induced NASH-like pathologies in wild-type mice, CuZn-SOD-deficient mice failed to show typical hepatic injuries, suggesting that CuZn-SOD deficiency prevented from MCD-diet induced by hepatic stress. Furthermore, we crossbred CuZn-SOD-deficient mice with ob/ob mice to investigate pathological role of obesity on hepatic CuZn-SOD deficiency. Interestingly, double mutant mice also failed to show apparent hepatic abnormalities, suggesting that CuZn-SOD deficiency does not accelerate hepatic pathologies induced by impaired leptin signaling and obesity.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy.2010
Author(s)
Kuwahara H., Horie T. Ishikawa S. Tsuda C., Kawakami S., Noda Y., Kaneko T., Tahara S., Tachibana T., Okabe M., Melki J., Takano R., Toda T., Morikawa D., Nojiri H., Kurosawa H., Shirasawa T., Shimizu T.
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Journal Title
Free Rad Biol Med 48
Pages: 1252-1262
Related Report
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[Journal Article] Conditional knockout of MnSOD targeted to type IIB skeletal muscle fibers increases oxidative stress and is sufficient to alter aerobic exercise capacity.2009
Author(s)
Lustgarten M., Jang Y., Liu Y., Muller F., Qi W., Steinhelper M., Brooks S., Larkin L. M., Shimizu T., Shirasawa T., McManus L., Bhattacharya A., Richardson A., Van Remmen H.
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Journal Title
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[Journal Article] Antioxidant, EUK-8, prevents murine dilated cardiomyopathy.2009
Author(s)
Kawakami S., Matsuda A., Sunagawa T., Noda Y., Kaneko T., Tahara S., Hiraumi Y., Adachi S., Matsui H., Ando K., Fujita T., Maruyama N., Shirasawa T., Shimizu T.
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Journal Title
Cir J 73
Pages: 2125-2134
NAID
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[Journal Article] Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice.2008
Author(s)
Hashizume K., Hirasawa M., Imamura Y., Noda S., Shimizu T., Shinoda K., Kurihara T., Noda K., Ozawa Y., Ishida S., Miyake Y., Shirasawa T., Tsubota K.
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Journal Title
Am J Pathol 172
Pages: 1325-1331
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