2007 Fiscal Year Final Research Report Summary
Study on hormone action using DHCR24-knock-out cells
| Project/Area Number |
18591017
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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 |
Endocrinology
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| Research Institution | Nagoya University |
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Principal Investigator |
KAMBE Fukushi Nagoya University, Res, Instit, Environ. Med, Assoc. Prof. (00211871)
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| Co-Investigator(Kenkyū-buntansha) |
SEO Hisao Nagoya University, Res, Instit, Environ. Med, Prof (40135380)
SAWADA Makoto Nagoya University, Res, Instit, Environ. Med, Prof (10187297)
CAO Xia Nagoya University, Res, Instit, Environ. Med, Assit. Prof (70432218)
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| Project Period (FY) |
2006 – 2007
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| Keywords | DHCR24 / ER stress / oxidative stress / hydrogen peroxide / tunicamycin / ASK-1 / p38 MAPK / JUK |
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| Research Abstract |
3β-Hydroxysteroid-A24 reductase(DHCR24) is an endoplasmic reticulum(ER) -resident, multifunctional enzyme that possesses anti-apoptotic and cholesterol-synthesizing activities. To clarify the molecular basis of the former activity, we investigated the effects of hydrogen peroxide(H_2O_2) on embryonic fibroblasts prepared from DHCR24-knockout mice(DHCR244- MEFs). H_2O_2 exposure rapidly induced apoptosis, which was associated with sustained activation of apoptosis signal-regulating kinase(ASK) -1 and stress-activated protein kinases, such as p38 mitogen-activated protein kinase(MAPK) and c-Jun N-terminal kinase(JNK). Complementation of the MEFs by adenovirus expressing DHCR24 attenuated the H_2O_2-induced kinase activation and apoptosis. Concomitantly, intracellular generation of reactive oxygen species(ROS) in response to H_2O_2 was also diminished by the adenovirus, suggesting a ROS-scavenging activity of DHCR24. Such anti-apoptotic effects of DHCR24 were duplicated in pheochromocytoma PC12 cells infected with adenovirus. In addition, it was found that DHCR24 exerted cytoprotective effects in the tunicamycin-induced ER stress by eliminating ROS. Finally, utilizing in vitro synthesized and purified proteins, DHCR24 and its C-terminal deletion mutant were found to exhibit high H_2O_2-scavenging activity, while the N-terminal deletion mutant lost such activity. These results demonstrate that DHCR24 can directly scavenge H_2O_2, thereby protecting cells from oxidative-stress-induced apoptosis
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Research Products
(56 results)
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[Journal Article] Long-term amiodarone treatment causes cardioselective hypothyroid-like alteration in gene expression profile2008
Author(s)
Shi, RQ, Lee, JK, Hayashi, Y, Takeuchi, Y, Kambe, F, Futaki, S, Seo, H, Murata, Y, Kodama, I
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Journal Title
European Journal of Pharmacology 578
Pages: 270-278
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Thyroid hormone activates AMP-activated protein kinase via intracellular calcium mobilization and activation of calcium/calmodulin-dependent protein kinase kinase-beta2008
Author(s)
Yamauchi, M, Kambe, F, Can, X, Lu, X, Kozaki, Y, Oiso, Y, Seo, H
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Journal Title
Molecular Endocrinology 22
Pages: 760-77
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice2008
Author(s)
Mirza, R, Hayasaka, S, Kambe, F, Maki, K, Kaji, T, Murata, Y, Seo, H
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Journal Title
British Journal of Dermatology 158(4)
Pages: 679-684
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Parathyroid hormone activates phosphoinositide 3 kinase-Akt-Bad cascade in osteoblast-like cells2007
Author(s)
Yamamoto, T, Kambe, F, Can, X, Lu, X, Ishiguro, N, Seo, H
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular cloning of prostaglandin EP3 receptors from canine sensory ganglia and their facilitatory action on bradykinin-induced mobilization of intracellular calcium2007
Author(s)
Kozaki, Y, Kamhe, F, Hayashi, Y, Ohmori, S, Seo, H, Kumazawa, T, Mizumura, K
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Journal Title
Journal of Neurochem 100
Pages: 163647
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential expression of cyclin-dependent kinase inhibitors, p27Kipl and p57Kip2, by corticotropin in rat adrenal cortex2006
Author(s)
Kobayashi, H, Kambe, F Imai, T, Hibi, Y, Kikumori T, Ohmori, S, Nakao, A, Seo, H
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Journal Title
Journal of Endocrinology 189
Pages: 671-679
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolde and insulin-Akt-Bad signaling2006
Author(s)
Lu, X, Kambe, F, Cao, X, Yoshida, T, Ohmori, S, Murakanri, K, Kaji, T, Ishii, T, Zadwomy, D, Seo, H
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Journal Title
Endocrinology 147(6)
Pages: 3123-3132
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DHCR24 is a hydrogen peroxide-scavenger, protecting cells from oxidative stress-induced apoptosis
Author(s)
Lu, X, Kambe, F, Can, X, Kozaki, Y, Kaji, T, Ishii, T, San, H
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Involvement of TR in T3 activation of AMPK2007
Author(s)
Yamauchi, M, Kambe, F, Can, X, Lu, X, Oiso, Y, Seo, H
Organizer
50th Annual Meeting of the Japan Thyroid Association
Place of Presentation
Kobe
Year and Date
2007-11-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Activation of AMPK by 13 via CaMKK-beta2007
Author(s)
Yamauchi, M, Kambe, F Yamauchi, M, Kambe, F, Can, X, Lu, X, Kozaki, Y, Oiso, Y, Seo, H
Organizer
The 80st Annual Meeting of the Japan Endocrine Society
Place of Presentation
Tokyo
Year and Date
2007-06-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 「研究成果報告書概要(欧文)」より2007
Author(s)
Hibi, Y, Kambe, F, Mizuno, Y, Seko, T, Ito, A, Yamamoto, H, Jinho, T, Tominaga, Y, Imai, T, Iwase, K, Seo, H
Organizer
The 80st Annual Meeting of the Japan Endocrine Society
Place of Presentation
Tokyo
Year and Date
2007-06-16
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[Presentation] 1'3 activates AMPK via intracellular Ca mobilization and activation of CaMKK-beta2007
Author(s)
Yamauchi, M, Kambe, F., Cao, X, Lu, X, Kozaki, Y, Oiso, Y, Seo, H
Organizer
89th Annual Meeting of the American Endocrine Society
Place of Presentation
Toronto
Year and Date
2007-06-05
Description
「研究成果報告書概要(欧文)」より
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[Presentation] DHCR24-/- mice demonstrate impaired maturation of the epidermis with an increased expression of aquaporin-3 (AQP3), affecting the epidermal hydration2007
Author(s)
Mirza, R, Hayasaka, S, Kambe, F, Maki, K, Kaji, T, Murata, Y, See, H
Organizer
68th Society for Investigative Dermatology Annual Meeting
Place of Presentation
Los Angels
Year and Date
2007-05-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Activation of AMPK by thyroid hormone2006
Author(s)
Yamauchi, M, Kambe, F, Can, X, Lu, X, Oiso, Y, Seo, H
Organizer
490 Annual Meeting of the Japan Thyroid Association
Place of Presentation
Takamatsu
Year and Date
2006-11-02
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Expression of PRKAR1a in adenoma of parathyroid glands in primary hyperparathyroidism2006
Author(s)
Hibi, Y, Seko, T, Ito, A, Imai, T, Tominaga, Y, Kambe, F, Seo, H, Iwase, K
Organizer
The 79st Annual Meeting of We Japan Endocrine Society
Place of Presentation
Kobe
Year and Date
2006-05-20
Description
「研究成果報告書概要(欧文)」より
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