Bupyoung Internal Medicine Clinic, Incheon, Korea.
Korean J Intern Med. 2011 Sep;26(3):314-9. doi: 10.3904/kjim.2011.26.3.314. Epub 2011 Sep 13.
BACKGROUND/AIMS: Hypoalbuminemia occurs frequently in renal transplant recipients immediately after renal transplantation. We studied the regulation of hepatic albumin synthesis by cyclosporin A (CsA) in Huh7 cells.
Huh7 cells were incubated with various concentrations of CsA for 4, 8, 16, and 24 hours. Albumin was measured in Huh7 cell-conditioned medium by sandwich enzyme-linked immunosorbent assay and Western blot. Albumin mRNA expression was analyzed by Northern blotting in CsA-treated cells.
CsA (10(-7)-10(-4) M) inhibited albumin synthesis in Huh7 cells in a dose- dependent manner. A Western blot analysis for albumin in the conditioned medium released from CsA-treated (10(-7)-10(-5) M) cells also showed significant inhibition of albumin synthesis in a dose-dependent manner. Vehicle (olive oil) did not affect albumin synthesis. In contrast, a Northern blot analysis revealed no inhibition of albumin mRNA expression by CsA at any time point from 1-24 hours, indicating that the inhibition of albumin synthesis occurred at the translational level.
Our results suggest that inhibition of hepatic albumin synthesis by high dose CsA contributes to the hypoalbuminemia in renal transplant recipients.
背景/目的:肾移植后,肾移植受者常出现低白蛋白血症。我们研究了环孢素 A(CsA)对 Huh7 细胞中肝白蛋白合成的调节作用。
用不同浓度的 CsA 孵育 Huh7 细胞 4、8、16 和 24 小时。夹心酶联免疫吸附试验和 Western blot 检测 Huh7 细胞条件培养基中的白蛋白。用Northern blot 分析 CsA 处理细胞中的白蛋白 mRNA 表达。
CsA(10(-7)-10(-4)M)以剂量依赖的方式抑制 Huh7 细胞中的白蛋白合成。CsA(10(-7)-10(-5)M)处理细胞释放的条件培养基中的白蛋白 Western blot 分析也显示白蛋白合成呈剂量依赖性显著抑制。载体(橄榄油)不影响白蛋白合成。相反,Northern blot 分析显示,在 1-24 小时的任何时间点,CsA 均未抑制白蛋白 mRNA 表达,表明白蛋白合成的抑制发生在翻译水平。
我们的结果表明,高剂量 CsA 抑制肝白蛋白合成导致肾移植受者低白蛋白血症。