Cyclosporin A inhibits mitochondrial biogenesis in Hep G2 cells
- Departrment of General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 (China)
- Department of Oncological Surgery, Central Hospital, Baotou, Inner Mongolia, 014040 (China)
- Neurology Department, Inner Mongolia North Heavy Industries Group Corp. Ltd Hospital, Third Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, 014030 (China)
- Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University (China)
Highlights: • Cyclosporine A (CsA) reduced the expressions of PGC-1α, NRF1 and TFAM. • CsA reduced mtDNA/nDNA, Mitochondrial mass, ATP, and cytochrome C oxidase activity. • Overexpression of PGC-1α prevented CsA-induced reduction in mitochondrial biogenesis. • CsA-induced reduction of PGC-1α expression was mediated by CREB. Dysregulation of mitochondrial biogenesis is associated with pathogenesis in many diseases, including liver diseases. Cyclosporine A (CsA), one of the most commonly used drug to treat many autoimmune diseases and to prevent allograft rejection after organ transplantation, has been reported to cause mitochondrial dysfunction. However, the cellular mechanisms underlying CsA on mitochondrial dysfunction remain at present not completely elucidated. In this study, we found that CsA reduced the expression of PGC-1α at both the mRNA and protein levels in HepG2 cells. Correspondingly, the expressions of its target genes NRF 1 and TFAM were reduced in response to CsA treatment. In addition, mtDNA/nDNA, mitochondria mass, ATP production, and cytochrome C oxidase activity were significantly reduced by treatment with CsA. Over-expression of PGC-1α was found to rescue the negative effect of CsA administration on mitochondrial biogenesis. Mechanistically, CREB was involved in the inhibitory effects of CsA in mitochondrial biogenesis.
- OSTI ID:
- 23127377
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 496; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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