• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification and their function of paraquat-induced unknown genes in rat lungs.

Research Project

Project/Area Number 13670439
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionKawasaki Medical School

Principal Investigator

TOMITA Masafumi  Kawasaki Medical School, Medical Toxicology, Associate Professor, 医学部, 助教授 (50113197)

Co-Investigator(Kenkyū-buntansha) HIDAKA Kazuo  Kawasaki Medical School, Biochemistry, Lecturer, 医学部, 講師 (00069064)
NISHIMATSU Shin-ichiro  Kawasaki Medical School, Molecular Biology, Lecturer, 医学部, 講師 (20222185)
NOHNO Tsutomu  Kawasaki Medical School, Molecular Biology, Associate Professor, 医学部, 助教授 (20098619)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsParaquat / Pulmonary injury / Oxidative stress / Differential display / gene expression / Free radical / cDNA array / Real-time PCR / differential display / superoxide / free radical / Clara cell / TAFIIB / Lpin2 / ラット
Research Abstract

The aim of the present work was to evaluate the implications for genes that are regulated by oxidative stress at the early stage of PQ exposure in rat lungs. Rats were treated with 20mg/kg PQ for 3 h, and the lungs were immediately excised. Significant pulmonary injury was observed after 2 weeks under our experimental conditions. 1)In the first year, we were particularly interested in two genes, TAFIIB and Lpin2. They were strongly visualized in Clara cells and in alveolar macrophages. These findings suggest the possibility that transcription levels and lipid metabolism are activated in Clara cells and in macrophages, resulting in their playing a crucial role at the onset of PQ-driven pulmonary injury. 2)In the second year, 19 differentiated clones were isolated by differential display-PCR method. Four clones were finally determined to be significantly affected. They were plasma phospholipid transfer protein(PLTP), lactrophiline, all-spectrin and one unknown gene. We showed the distribution of mRNA expression of lactrophiline in lung tissues. 3)In the third year, using cDNA array membrane, we found that PQ exposure gave 29 genes differentially expressed(>1.5-fold). Some positive genes were further validated and quantitated with real-time RT-PCR. The expressions of PDGF, thioredoxin, glutathione S-transferase, SOD were significantly up-regulated, suggesting that the oxygen free radicals were major contributors to the onset of PQ poisoning. In addition, some CYP members (CYP2C6,2C7,2C12,2C13) were remarkably affected. The stimulation of expressions was peculiar to lungs, and not to liver and kidneys. These results suggest that they are involved in the onset of PQ-induced serious pulmonary injury.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] M.Tomita, T.Okuyama, K.Hidaka, T.Nohno et al.: "Early differential gene expression of rat lung after exposure to paraquzat."Free Rad.Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Adachi, K.Ishii, M.Tomita et al.: "Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury."Arch.Toxicol.. 77. 353-357 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ishii, J.Adachi, M.Tomita et al.: "Oxysterols as indices of oxidative stress in man after paraquat ingestion."Free Rad.Res.. 36. 163-168 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Nohno, T.Okuyama, S.Nishimatsu, J.Adachi: "Paraquat-induced gene expression in rat lung tissues using a differential display reverse transcription-polymerase chain reaction."Arch.Toxicol.. 76. 530-537 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Nohno, T.Okuyama, T.Hidaka, W.Xu: "Hypervariable locus of the 3'-flanking region of the neurotensin receptor gene : an effective region for personal identification in forensic practice."Forensic Sci.Int.. 127. 119-127 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Okuyama, T.Ishikawa et al.: "The role of nitric oxide in paraquat- induced cytotoxicity in the human A549 lung carcinoma cell line."Free Rad.Res.. 34. 193-202 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Okuyama, K.Hidaka, T.Nohno et al.: "Early differential gene expression of rat lung after exposure to paraquat."Free Rad.Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Adachi, K.Ishii, M.Tomita et al.: "Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury."Arch.Toxicol.. 77. 353-357 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ishii, J.Adachi, M.Tomita et al.: "Oxysterols as indices of oxidative stress in man after paraquat ingestion."Free Rad.Res.. 36. 163-168 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Nohno, T.Okuyama, S.Nishimatsu, J.Adachi: "Paraquat-induced gene expression in rat lung tissues using a differential display reverse transcription-polymerase chain reaction."Arch.Toxicol.. 76. 530-537 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Nohno, T.Okuyama, T.Hidaka, W.Xu: "Hypervariable locus of the 3'-flanking region of the neurotensin receptor gene : an effective region for personal identification in forensic practice."Forensic Sci.Int.. 127. 119-127 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomita, M., Okuyama, T., Ishikawa, T., Hidaka, K., Nohno, T.: "The role of nitric oxide in paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line."Free Rad.Res.. 34. 193-202 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Tomita, T.Okuyama, K.Hidaka, T.Nohno et al.: "Early differential gene expression of rat lung after exposure to paraquat"Free Rad.Res.. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Adachi, K.Ishii, M.Tomita et al.: "Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury"Arch.Toxicol.. 77. 353-357 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 富田正文, 日高和夫, ら: "個人識別におけるニューロテンシンレセプターの多型性について"DNA多型. 11. 91-94 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 勝山博信, 富田正文, 日高和夫, 河合俊夫: "ビタミンDレセプター多型と日常生活習慣との関連"DNA多型. 11. 212-214 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 日高和夫, 富田正文 ら: "カーバメート系農薬分解酵素の活性測定法と酵素の精製"川崎医会誌. 29. 7-12 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Tomita, T.Nohno, S.Nishimatsu et al.: "Paraquat-induced gene expression in rat lung tissues using a differential display reverse transcription-polymerase chain reaction"Arch. Toxicol.. 76・9. 530-537 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Ishii, J.Adachi, M.Tomita et al.: "Oxysterols As Indices of Oxidative Stress in Man Paraquant Ingestion"Free Rad. Res.. 36. 163-168 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Tomita, T.Nohno, K.Hidaka: "Hypervariable locus of the 3'flanking region of the neurotensin receptor gene: an effective region for personal identification in forensic practice"Forensic Science Int.. 127・1-2. 119-127 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Tomita, T.Nohno, S.Nishimatsu, K.Hidaka et al.: "Identification and characterization of mRNAs differentially expressed in rat lungs exposed to paraquat"Abstract of the 11th Meeting of the Society for Free Radical Research International. 167-167 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 日高和夫, 富田正文: "有機リン農薬分解酵素の活性測定法の確立と遺伝子多型の解析"DNA多型. 10. 37-41 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] J.Adachi, K.Ishii, M.Tomita et al.: "Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury"Arch. Toxicol.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Tomita, T.Nohno et al.: "The role of nitric oxide in paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line"FreeRad. Res.. 34. 193-202 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Hidaka, Y.Watanabe, M.Tomita et al.: "Gene analysis of genomic DNA from stored serum by polymerase chain reaction : identification of three missense mutations in patients with cholinesterasemia and ABO genotyping"Clinica Chimica Acta. 303. 61-67 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 富田正文, 奥山敏子: "ヒトNeurotensin receptor遺伝子の3'-flanking領域における高変異ローカスについて"DNA多型. 9. 226-229 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Ishii, J.Adachi, M.Tomita et al.: "Enhance lipid peroxidation in human paraquat poisoning"Abstract of the 7th INPALMS. 189-189 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] J.Adachi, M.Tomita et al.: "Increased lipid peroxidation in rat administered paraquat"Abstract of the 7th INPALMS. 190-190 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 富田正文: "パラコートで発現が促進されるラット肺での遺伝子について"日法医誌. 55・1. 67-67 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi