Cyclosporine A: impact on mitochondrial function in endothelial cells
Sabine Illsinger1, Nils Janzen, Thomas Lücke
1Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Clinical Transplantation
|July 17, 2010
Summary
Cyclosporine A (CSA) impairs mitochondrial function, affecting fatty acid oxidation and respiratory enzymes in endothelial cells. Cellular energy is partially maintained by glycolysis, but CSA toxicity may impact organs with high energy demands.
Area of Science:
- Mitochondrial Biology
- Cellular Metabolism
- Immunopharmacology
Background:
- Cyclosporine A (CSA) is an effective immunosuppressant in transplantation.
- CSA can cause vascular and neurological side effects.
- Mitochondrial dysfunction is a potential mechanism for CSA's adverse effects.
Purpose of the Study:
- To investigate the impact of CSA on mitochondrial and glycolytic function in human umbilical vein endothelial cells.
- To assess CSA's effects on key metabolic pathways and cellular energy production.
Main Methods:
- Measurement of fatty acid oxidation (FAO), respiratory chain (RC) complex activities, and citrate synthase (CS).
- Analysis of lactate/pyruvate ratios and energy-rich phosphates.
- Assay of glycolytic enzyme activities and assessment of cellular toxicity via LDH leakage.
Main Results:
- CSA significantly reduced global FAO, RC complexes (1+3, 4, 5), and CS activity.
- Lactate/pyruvate ratios increased, indicating a shift towards glycolysis.
- No significant impairment of glycolytic enzymes or energy charges was observed, with toxicity only at high CSA concentrations.
Conclusions:
- CSA-induced alterations in mitochondrial function (impaired FAO and RC enzymes) contribute to its toxicity.
- Cytosolic energy production via glycolysis can partially compensate for mitochondrial dysfunction.
- These metabolic effects in endothelial cells may extend to other organs with high oxidative energy demands.
