Molecular mechanism for aging control

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390085
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Juntendo University
• Principal Investigator: SHIRASAWA Takuji Juntendo University, 大学院・医学研究科, 客員教授 (80226323)
• 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)
• Project Period (FY): 2008 – 2010
• Keywords: 加齢 / 酸化ストレス / 脂肪肝 / NASH / モデルマウス

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.

Research Products

• [Journal Article] Superoxide dismutase deficiency enhances superoxide levels in brain tissues during oxygenation and hypoxia-reoxygenation. (2011)
  • Author(s): Sasaki T., Shimizu T., Koyama T., Sakai M., Uchiyama S., Kawakami S., Noda Y., Shirasawa T., Kojima S.
  • Journal Title: J Neurosci Res 89 Pages: 601-610
• [Journal Article] Model mice for tissue-specific deletion of the manganese superoxide dismutase (Mn-SOD) gene. (2010)
  • Author(s): Shimizu T., Kawakami S., Nojiri N., Shirasawa T.
  • Journal Title: Geriatr Gerontol Int 10 Pages: S70-S79
• [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.
  • Journal Title: Free Rad Biol Med 48 Pages: 1252-1262
• [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.
  • Journal Title: Am J Physiol 297 Pages: C1520-1532
• [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.
  • Journal Title: Cir J 73 Pages: 2125-2134
• [Journal Article] Skin atrophy in cytoplasmic SOD-deficient mice and its complete recovery using a vitamin C derivative. (2009)
  • Author(s): Murakami K., Inagaki J., Saito M., Ikeda Y., Tsuda C., Noda Y., Kawakami S., Shirasawa T., Shimizu T.
  • Journal Title: Biochem Biophys Res Commun 382 Pages: 457-61
• [Journal Article] Clk-1 deficiency induces apoptosis associated with mitochondrial dysfunction in mouse embryos. (2008)
  • Author(s): Takahashi M., Shimizu T., Moriizumi E., Shirasawa T.
  • Journal Title: Mech Ageing Dev 129 Pages: 291-298
• [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.
  • Journal Title: Am J Pathol 172 Pages: 1325-1331
• [Presentation] Antioxidant, EUK-8, prevents murine dilated cardiomyopathy. (2010)
  • Author(s): Shirasawa T., Kawakami S., Shimizu T.
  • Organizer: Gordon Research Conferences
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 20100822-20100827
• [Remarks] ホームページ等