Cyclosporin a inhibits albumin synthesis in Huh7 cells.
OBJECTIVE
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.
Bupyoung Internal Medicine Clinic, Incheon, Korea.
Youn Joo
YJ
Jeon
Yong Soo
YS
Kim
D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D034141:Hypoalbuminemia / Q000139:chemically induced / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D012709:Serum Albumin; D016572:Cyclosporine