Molecular mechanisms underlying HIF-1 activation by fatty acid-bearing albumin and renal protective effect by its regulation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460218
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Osaka University of Pharmaceutical Sciences
• Principal Investigator: NAGAI Junya 大阪薬科大学, 薬学部, 教授 (20301301)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 脂肪酸 / アルブミン / 尿細管上皮細胞 / HIF-1 / GLUT1 / BCRP

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.

Free Research Field

薬物動態学