Molecular mechanisms underlying HIF-1 activation by fatty acid-bearing albumin and renal protective effect by its regulation
| Project/Area Number |
26460218
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
NAGAI Junya 大阪薬科大学, 薬学部, 教授 (20301301)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脂肪酸 / アルブミン / 尿細管上皮細胞 / HIF-1 / GLUT1 / BCRP / 低酸素誘導因子 / 腎尿細管 / トランスポーター / 腎近位尿細管上皮細胞 / 低酸素誘導因子HIF-1 / 乳癌耐性タンパク質BCRP / エンドサイトーシス |
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| Outline of Final Research Achievements |
In this study, we performed analysis to identify fatty acid which plays an important role in HIF-1 activation by fatty acid-bearing albumin exposure and to examine an involvement of PPAR gamma in fatty acid-bearing albumin-induced HIF-1 activation in HK-2 cells.
Treatment with palmitic acid and oleic acid had no significant effect on GLUT-mediated transport activity, which is enhanced by HIF-1 activation, while the activity of GLUT was increased by treatment with arachidonic acid. These results indicated that arachidonic acid is involved in albumin-induced HIF-1 activation. We also observed induction of HIF-1 alpha, GLUT1 and BCRP mRNA expression by treatment with a PPAR gamma agonist pioglitazone. In addition, pioglitazone increased transport activity of GLUT and BCRP in a concentration-dependent manner. These findings suggested that PPAR gamma induced HIF-1 activation, resulting in enhanced transporter activity of GLUT and BCRP, HIF-1 target gene products.
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Report
(4 results)
Research Products
(19 results)
