| Project/Area Number |
12670550
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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 |
Respiratory organ internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
MATSUSE Takeshi Yokohama City University Medical Center, Dept. of Pulmonary Medicine, Professor, 医学部・附属病院, 教授 (90199795)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Michiaki Dokkyo University School of Medicine, Dept. of Microbiology, Professor, 医学部, 教授 (80199702)
MIYASHITA Akira Yokohama City Medical Center, Dept. of Pulmonary Medicine, Lecturer, 医学部・附属病院, 講師 (40239398)
SHIRAI Akira Yokohama City University Medical Center, Center of Infectious disease, Associate Professor, 医学部・附属病院, 助教授 (40244488)
TERAMOTO Shinji International University of Health and Welfare, Medical Research Center, Associate Professor, 保健学部, 助教授 (50282629)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Xenobiotic enzyme / Glutathione S-transferase P1 / Apoptosis / Necrosis / cigarette smoke / pulmonary emphysema / COPD |
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| Research Abstract |
Cigarette smoking is thought to be a major risk factor in various lung diseases, including chronic obstructive pulmonary disease. In this study, we investigated the viability of human lung fibroblast-derived HFL-1 cells in different concentrations of the cigarette smoke extract (CSE). CSE induced apoptosis at lower concentrations (10-25 %) and necrosis at higher concentrations (50-100 %). We also examined effects of glutathione S-transferase P1 (GSTP1), one of the xenobiotic metabolizing and antioxidant enzymes in the lung, against the cytotoxicity of CSE. Our results indicated that the level of HFL-1 cell death was decreased upon transfection of a GSTP1 expression vector and was increased by GSTP1 antisense vector transfection. Therefore, transient over-expression and under-expression of GSTP1 appeared to inhibit and enhance the cytotoxic effects of CSE on HFL-1, suggesting that GSTP1 may have protective effects against cigarette smoke in the airway cells. In addition, we examined the effects of chronic smoke inhalation on the function and morphology of lungs in mice lacking glutathione S-transferases P1/P2 (GSTP1). After 16 weeks of cigarette smoke exposure, a significant airspace size enlargement along with a leftward shift of the pressure-volume (P-V) curve was observed in GSTP1/2 null mice but not in control mice, when compared with the same strain of mice with air exposure. The results suggest that disruption of glutathione S-transferases pi class is susceptible to cigarette smoke-induced pulmonary emphysema in mice.
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