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Cyclosporine A: impact on mitochondrial function in endothelial cells
Author(s) -
Illsinger Sabine,
Janzen Nils,
Lücke Thomas,
Bednarczyk Jolanthe,
Schmidt KarlHeinz,
Hoy Ludwig,
Sander Johannes,
Das Anibh M.
Publication year - 2011
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2010.01301.x
Subject(s) - glycolysis , medicine , respiratory chain , lactate dehydrogenase , mitochondrial respiratory chain , mitochondrion , phosphofructokinase , toxicity , oxidative phosphorylation , biochemistry , hexokinase , mitochondrial toxicity , endocrinology , metabolism , pharmacology , enzyme , biology
Illsinger S, Janzen N, Lücke T, Bednarczyk J, Schmidt K‐H, Hoy L, Sander J, Das AM. Cyclosporine A: impact on mitochondrial function in endothelial cells.
Clin Transplant 2011: 25: 584–593. © 2010 John Wiley & Sons A/S. Abstract: Introduction: Although cyclosporine A (CSA) is considered to be an efficient immunosuppressive compound in transplantation, vascular side effects like arterial hypertension, neurologic complications and other adverse reactions occur. Interference of CSA with mitochondrial function may be responsible for these side effects. Methods: We evaluated the effect of CSA on mitochondrial and glycolytic function by measuring fatty acid oxidation (FAO), activities of respiratory chain complexes (RC) and citratesynthase (CS), lactate/pyruvate‐ratios, energy‐rich phosphates as well as activities of some glycolytic enzymes in human umbilical vein endothelial cells. Results: After 48 h of CSA incubation, global FAO, RC‐complexes 1 + 3; 4 and 5 as well as CS were compromised while energy charges were not reduced. Lactate/pyruvate‐ratios increased; cellular lactate dehydrogenase (LDH)‐, hexokinase‐ and phosphofructokinase‐activities were not impaired by CSA. Moderate cellular toxicity, assessed by LDH leakage, appeared only at the highest CSA concentration. Conclusion: Part of CSA toxicity may arise from alterations in mitochondrial function as judged by impaired FAO and respiratory chain enzymes. To some extent, energy balance seems to be maintained by cytosolic energy production. Although only demonstrated for endothelial cells, it is conceivable that such effects will alter energy metabolism of different organs with high oxidative energy demands.