Elucidation of signal transduction pathway related to a radiation resistance of the nematode

• Project/Area Number: 25340037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Tokai University
• Principal Investigator: ISHII Naoaki 東海大学, 医学部, 教授 (60096196)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 放射線 / 老化 / 活性酸素 / C. elegans / ホルミシス / シグナル伝達経路 / MXL-3 / SKN-1 / シグナル伝達 / 酸化ストレス / 飢餓ストレス / ホルミシス効果 / 放射線障害 / 耐性幼虫 / 寿命 / mxl-3

Outline of Final Research Achievements

We have previously shown that X-ray irradiation extends lifespan and up-regulates the expression of mxl-3 at a dauer larval stage of the nematode Caenorhabditis elegans.
It is well known that reactive oxygen species generated from radiation react with water in vivo contributes to the cellular damages and it is reported that MXL-3 binds to SKN-1 related to oxidative stress. In fact, mxl-3 mRNA levels was up-regulated in wild type worms exposed to paraquat and then the mxl-3 mutant was hypersensitive to paraquat and is short lived under oxygen stress of high concentration.Our result raise the possibility that MXL-3 is involved in response to oxidative stress in collaboration with SKN-1.

Research Products

• [Journal Article] A combination of mitochondrial oxidative stress and excess fat/calorie intake accelerates steatohepatitis by enhancing hepatic CC chemokine production in mice. (2016)
  • Author(s): Moro T, Nakao S, Sumiyoshi H, Ishii T, Miyazawa M, Ishii N, Sato T, Iida Y, Okada Y, Tanaka M, Hayashi H, Ueha S, Matsushima K, Inagaki Y
  • Journal Title: PLoS ONE Volume: 11 Issue: 1 Pages: e0146592-e0146592
  • DOI: 10.1371/journal.pone.0146592
  • Peer Reviewed / Open Access
• [Journal Article] Infertility and recurrent miscarriage with complex II deficiency-dependint mitochondrial oxidative stress in animal models (2016)
  • Author(s): Ishii T, Yasuda K, Miyazawa M, Mitsushita J, Johnson TE, Hartman PS, Ishii N
  • Journal Title: Mechanisms of Ageing and Development Volume: 155 Pages: 22-35
  • DOI: 10.1016/j.mad.2016.02.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Preparation of clinically usefull sennoside-reduced Rhubarb (2016)
  • Author(s): Arai M, Nakada Y, Kajiwara K, Kimura M, Ishii N
  • Journal Title: Tokai J. Exp. Clin. Ned. Volume: 41 Pages: 24-29
  • Peer Reviewed
• [Journal Article] Retrospective on nine years of the Anti-Aging Health Check-ups in Tokai University Tokyo Hospital: From establishment to future (2015)
  • Author(s): Nishizaki Y, Yamada C, Kishimoto N, Shiozawa H, Takeda A, Agata T, Kuroda E, Kubo A, Kuwahira I, Ishii N
  • Journal Title: Health Evaluation and Promotion Volume: 42 Issue: 4 Pages: 465-470
  • DOI: 10.7143/jhep.42.465
  • NAID: 130005096321
  • ISSN: 1347-0086, 1884-4103
  • Peer Reviewed
• [Journal Article] Longitudinal trajectories of adiponectin and HDL-C levels over a 3-year survey within the anti-aging health checkup system at Tokai University Tokyo Hospital (2015)
  • Author(s): Yamada C, Kishimoto N, Yukumatsu N, Takeda A, Ogawta T, Kikuchi E, Kuroda E, Kubo A, Ishii N, Nishizaki Y
  • Journal Title: Health Evaluation and Promotion Volume: 42 Issue: 4 Pages: 444-449
  • DOI: 10.7143/jhep.42.444
  • NAID: 130005096318
  • ISSN: 1347-0086, 1884-4103
  • Peer Reviewed
• [Journal Article] Ethyl methanesulfonate induces mutations in Caenorhabditis elegans embryos at a high frequency. (2014)
  • Author(s): (1)Hartman PS, Barry J, Finstad W, Khan N, Tanaka M, Yasuda K, Ishii N.
  • Journal Title: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Volume: 766-767 Pages: 44-48
  • DOI: 10.1016/j.mrfmmm.2014.05.011
  • Peer Reviewed
• [Journal Article] Evaluating “Cosmetic Therapy” by Using Near-Infrared Spectroscopy. (2014)
  • Author(s): (2)Ikeuchi M, Saruwatari K, Takeda Y, Shimoda M, Nakashima A, Inoue M, Oroguchi T, Ishii N, Yoshii F, Haida M.
  • Journal Title: World Journal of Neuroscience Volume: 4 Pages: 194-201
  • Peer Reviewed
• [Journal Article] Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia thatleads to recurrent abortion (2014)
  • Author(s): Ishii T, Miyazawa M, Takanashi Y, Tanigawa M, Yasuda K, Onouchi H, Kawabe N, Mitsushita J, Hartman PS, Ishii N
  • Journal Title: Redox Biology Volume: 2 Pages: 679-685
  • Peer Reviewed
• [Journal Article] Model animals for the study of oxidative stress from complex II (2013)
  • Author(s): Takamasa Ishii
  • Journal Title: Biochem. Biophys. Acta. Volume: 1827 Issue: 5 Pages: 588-597
  • DOI: 10.1016/j.bbabio.2012.10.016
  • Peer Reviewed
• [Presentation] 老化のシグナル (2015)
  • Author(s): 石井直明
  • Organizer: 心血管代謝週間2015
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市中央区）
  • Year and Date: 2015-12-10
  • Invited
• [Presentation] Oxidative stress response of a transcription factor MXL-3 in the nematode C. elegans (2015)
  • Author(s): Takahashi K, Yasuda K, Ishii T, Sasagawa N, Hartman P, Ishii N
  • Organizer: C. elegans 20th International Meeting
  • Place of Presentation: UCLA, California, USA
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Presentation] 線虫C. elegansのMXL-3転写因子の酸化ストレス応答 (2015)
  • Author(s): 高橋航大、安田佳代、石井恭正、笹川昇、石井直明
  • Organizer: 日本基礎老化学会第38回大会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市西区みなとみらい）
  • Year and Date: 2015-06-12
• [Presentation] 酸化ストレスと老化のモデル研究 (2014)
  • Author(s): 石井恭正，安田佳代，石井直明
  • Organizer: 第66回日本皮膚科学会西部支部学術大会
  • Place of Presentation: 高松
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] ミトコンドリア複合体II電子伝達異常に起因する酸化ストレスと生体の加齢変容 (2014)
  • Author(s): 石井恭正，宮沢正樹，安田佳代，石井直明
  • Organizer: 日本ミトコンドリア学会-日本基礎老化学会Joint Meeting
  • Place of Presentation: 東京 東海大学高輪キャンパス
  • Year and Date: 2014-10-25
• [Presentation] Age-dependent redox regulations with mitochondrial reactive oxygen species in hippocampal regions (2014)
  • Author(s): Ishii T, Takanashi Y, Miyazawa M, Yasuda K, Hartman PS, Ishii N
  • Organizer: The 2014 Cold Spring Harbor Laboratory meeting on Molecular Genetics of Aging
  • Place of Presentation: Cold Spring Harbor Laboratory、USA
  • Year and Date: 2014-09-29 – 2014-10-03
• [Presentation] ミトコンドリア酸化ストレスによる脳内グリア環境の加齢変化 (2014)
  • Author(s): 石井恭正，高梨由美，宮沢正樹，安田佳代，石井直明
  • Organizer: 第67回日本酸化ストレス学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] ミトコンドリア酸化ストレスに惹起される脳内環境の加齢変化おｔ記憶障害 (2013)
  • Author(s): 石井恭正、高梨由美、柳原倫太郎、浅利真司、安田佳代、石井直明
  • Organizer: 日本基礎老化学会
  • Place of Presentation: 大阪中之島センター
• [Presentation] The mechanism of longevity with hormesis by the low dose X ray-irradiation in C. elegans (2013)
  • Author(s): Hayashi S, Yasuda K, Ishii N, Ishii T
  • Organizer: The 20th IAGG world congress of genrontology and geriatorics
  • Place of Presentation: Seoul, Korea
• [Book] Aging mechanisms: Longevity, metabolism, and brain aging (2015)
  • Author(s): Ishii N, Ishii T, Hartman PS
  • Total Pages: 439
  • Publisher: Springer
• [Book] アンチエイジング読本 (2015)
  • Author(s): 石井直明
  • Total Pages: 157
  • Publisher: 東海教育研究所
• [Book] 老化の生物学 (2014)
  • Author(s): 石井恭正，石井直明
  • Total Pages: 351
  • Publisher: 化学同人