Fatty acid-bearing albumin but not fatty acid-depleted albumin induces HIF-1 activation in human renal proximal tubular epithelial cell line HK-2.
Fatty acid-bearing albumin but not fatty acid-depleted albumin induces HIF-1 activation in human renal proximal tubular epithelial cell line HK-2.
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DOI：
10.1016/j.bbrc.2014.05.146
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发表时间：
2014-07
影响因子：
3.1
通讯作者：
J. Nagai;A. Yamamoto;Yuki Katagiri;R. Yumoto;M. Takano
中科院分区：
文献类型：
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作者：
J. Nagai;A. Yamamoto;Yuki Katagiri;R. Yumoto;M. Takano
最近，我们发现白蛋白超载诱导人肾小管上皮细胞系HK-2中转录因子缺氧诱导因子-1 α（HIF-1α）蛋白和几个HIF-1靶基因的表达。在这项研究中，白蛋白结合的脂肪酸在白蛋白诱导的HIF-1激活的作用进行了研究。含脂肪酸的人血清白蛋白[FA（+）HSA]处理对HIF-1α蛋白表达的增强作用远大于去脂肪酸的人血清白蛋白[FA（-）HSA]处理。FA（+）HSA处理以浓度依赖性方式诱导HIF-1靶基因mRNA，如葡萄糖转运蛋白1（GLUT 1）、甘油醛3-磷酸脱氢酶（GAPDH）和乳腺癌耐药蛋白（BCRP）的mRNA，而FA（-）HSA未引起这些mRNA的显著增加。与GLUT 1 mRNA、GLUT 1蛋白表达和GLUT抑制剂细胞松弛素B敏感的[3 H]葡萄糖摄取活性增加一致，FA（+）HSA处理显著增强，但FA（−）HSA处理不增强。这些发现表明，与白蛋白结合的脂肪酸在白蛋白诱导的HIF-1活化中起着至关重要的作用，随后HIF-1靶基因表达和蛋白产物活性发生变化。
Recently, we found that albumin overload induces expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) protein and several HIF-1 target genes in human renal proximal tubular epithelial cell line HK-2. In this study, the role of albumin-bound fatty acids in the albumin-induced HIF-1 activation was studied. The enhancing effect of fatty acid-bearing human serum albumin [FA(+)HSA] treatment on HIF-1α protein expression was much greater than that of fatty acid-depleted human serum albumin [FA(−)HSA] treatment. The FA(+)HSA treatment induced HIF-1 target gene mRNAs such as those of glucose transporter 1 (GLUT1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and breast cancer resistance protein (BCRP) in concentration-dependent manners, while FA(−)HSA caused no significant increases in these mRNAs. Consistent with increased GLUT1 mRNA, GLUT1 protein expression and GLUT inhibitor cytochalasin B-sensitived-[3H]glucose uptake activity were significantly enhanced by treatment with FA(+)HSA, but not with FA(−)HSA. These findings indicate that fatty acids bound to albumin play a crucial role in albumin-induced HIF-1 activation followed by changes in HIF-1 target gene expression and protein product activity.