کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4280284 | 1611556 | 2010 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Cyclosporine A–protection against microvascular hyperpermeability is calcineurin independent Cyclosporine A–protection against microvascular hyperpermeability is calcineurin independent](/preview/png/4280284.png)
BackgroundMitochondria-mediated apoptotic signaling contributes to microvascular hyperpermeability. We hypothesized that cyclosporine A (CsA), which protects mitochondrial transition pores, would attenuate hyperpermeability independent of its calcineurin inhibitory property.MethodsHyperpermeability was induced in microvascular endothelial cell monolayers using proapoptotic BAK or active caspase-3 after CsA or a specific calcineurin inhibitor, calcineurin autoinhibitory peptide (CIP), treatment. Permeability was measured based on fluorescein isothiocyanate–albumin flux across the monolayers. Mitochondrial transmembrane potential (MTP) was determined using 5,5′,6,6′-tetrachoro-1,1′,3,3′-tetraethylbenzimidazolyl carbocyanine iodide. Mitochondrial release of cytochrome c was measured using an enzyme-linked immunosorbent assay and caspase-3 activity fluorometrically.ResultsCsA-attenuated (10 nmol/L) but not CIP-attenuated (100 μmol/L) BAK induced hyperpermeability (P < .05), CsA- but not CIP-attenuated BAK induced a decrease in MTP and an increase in cytochrome c levels and caspase-3 activity (P < .05). CsA and CIP were ineffective against caspase-3–induced hyperpermeability.ConclusionsCsA attenuated hyperpermeability by protecting MTP, thus preventing mitochondria-mediated apoptotic signaling. The protective effect of CsA is independent of calcineurin inhibition.
Journal: The American Journal of Surgery - Volume 199, Issue 4, April 2010, Pages 542–548