Project/Area Number |
14370328
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
|
Research Institution | Kobe University |
Principal Investigator |
CHIHARA Kazuo Kobe University, Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (00107955)
|
Co-Investigator(Kenkyū-buntansha) |
IGUCHI Genzou Kobe University, Hospital, research associate, 医学部附属病院, 助手 (60346260)
TAKAHASHI Yutaka Kobe University, Graduate School of Medicine, research associate, 大学院・医学系研究科, 助手 (70301281)
OKIMURA Yasuhiko Kobe University, School of Medicine, associate professor, 医学部, 助教授 (30204100)
飯田 啓二 神戸大学, 大学院・医学系研究科, 助手 (80324911)
|
Project Period (FY) |
2002 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥10,500,000 (Direct Cost: ¥10,500,000)
|
Keywords | growth hormone / signal transduction / anti-aging effect / adipocyte / 成人成長ホルモン欠損症 / 老化 / ミトコンドリア |
Research Abstract |
To clarify the mechanism of anti-aging effect of growth hormone (GH), mRNA levels in response to hGH were examined with differential display and DNA micro array in GH-targeting cells including vascular smooth muscle cell (VSMC), hepatocytes, and adipocytes. In VSMC, hGH increased cytochrome oxidase subunit II/III mRNA in addition to several unknown mRNAs. The mRNA for mitochondria transcription factor I (mtTFI) that stimulates the expression of cytochrome oxidase subunit II/III was up-regulated by hGH. Pretreatment with JAK2 inhibitor AG490 and a MEK inhibitor PD98059 suppressed mtTFI expression and pretreatment with a PI3 kinase inhibitor wortomannin did not, suggesting that hGH increases mtTFI mRNA levels through JAK2 and MEK signaling in VSMC. This finding afford into the relation of GH and mitochondria. The regulatory mechanism of GH on the mtTFI gene expression is ongoing. In adipocytes, hGH increased several unknown mRNA levels. Some of them increased along with adipocyte differentiation. Expression pattern and homology search suggested some of the GH-induced proteins might play an important role in GH action. Knock out mice of the genes are now being produced to clarify their physiological significance.
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