Cyclosporin a inhibits albumin synthesis in Huh7 cells

Korean J Intern Med. 2011 Sep;26(3):314-9. doi: 10.3904/kjim.2011.26.3.314. Epub 2011 Sep 13.

Abstract

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.

Methods: 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.

Results: 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.

Conclusions: Our results suggest that inhibition of hepatic albumin synthesis by high dose CsA contributes to the hypoalbuminemia in renal transplant recipients.

Keywords: Albumins; Cyclosporin A; Hypoalbuminemia; Kidney transplantation.

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Culture Media, Conditioned / metabolism
  • Cyclosporine / pharmacology*
  • Cyclosporine / toxicity
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoalbuminemia / chemically induced
  • Hypoalbuminemia / metabolism
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / toxicity
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • RNA, Messenger / metabolism
  • Serum Albumin / genetics
  • Serum Albumin / metabolism*
  • Time Factors

Substances

  • Culture Media, Conditioned
  • Immunosuppressive Agents
  • RNA, Messenger
  • Serum Albumin
  • Cyclosporine