Effect of tacrolimus on energy metabolism in human umbilical endothelial cells.
Summary of "Effect of tacrolimus on energy metabolism in human umbilical endothelial cells."
Background: Tacrolimus has a wide spectrum of adverse effects, including neurotoxic and vascular events. Vascular dysfunction due to interference of tacrolimus with mitochondrial function in endothelial cells may contribute to these adverse reactions. Material/Methods: We evaluated the impact of clinically relevant tacrolimus concentrations after 48 hours on energy metabolism in cultured human umbilical vein endothelial cells (HUVEC): Global fatty acid oxidation (FAO), activities of respiratory chain complexes I-V (RC), citratesynthase (CS), glycolytic enzymes and energy rich phosphates were measured. Results: RC-complexes II+III were significantly compromised at 100 nmol/L and CS at 10, 25 and 50 nmol/L, while global FAO was not significantly impaired. Cellular lactate-dehydrogenase (LDH)-, hexokinase- and phosphofructokinase-activities were not altered; AMP levels increased after 48 hours at 200 nmol/L while energy charges remained stable. No cellular toxicity, assessed by light microscopy and LDH leakage was observed even at highest tacrolimus concentrations. Conclusions: Tacrolimus partially impaired mitochondrial function in HUVEC at the level of RC-complexes II+III and CS. Part of tacrolimus toxicity and vascular dysfunction may arise from these metabolic alterations. To some extent, energy balance could be maintained by FAO and cytosolic energy production; energy consumption might be economized. Although only demonstrated for endothelial cells, it is conceivable that such effects will alter energy metabolism in different tissues with high oxidative demands.
Affiliation
Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School, Hannover, Germany and Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Journal Details
This article was published in the following journal.
Name: Annals of transplantation : quarterly of the Polish Transplantation Society
ISSN: 1425-9524
Pages: 68-75
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21716189
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Bioelectric Energy Sources
Electric power supply devices which convert biological energy, such as chemical energy of metabolism or mechanical energy of periodic movements, into electrical energy.
Energy Metabolism
The chemical reactions involved in the production and utilization of various forms of energy in cells.
Tacrolimus Binding Protein 1a
A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
Umbilical Veins
Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.
Umbilical Arteries
Specialized arterial vessels in the umbilical cord. They carry waste and deoxygenated blood from the FETUS to the mother via the PLACENTA. In humans, there are usually two umbilical arteries but sometimes one.
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