RETRACTED: NCX‐4016, a nitric oxide‐releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial function

Authors:
Open Access
Publisher website
Google Scholar
Abstract
We investigated the effect of a nitric oxide (NO)‐releasing derivative of aspirin (NCX‐4016) on a mitochondria‐dependent model of apoptosis in human umbilical endothelial cells (HUVEC). Exposure of HUVEC to staurosporine caused a progressive fall in mitochondrial membrane potential (∆ψ m ) and apoptosis. Exposure to an NO donor, ( z )‐1‐[2‐(2‐aminoethyl)‐ N ‐(2ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA‐NO), caused an early (1–3h) hyperpolarization of ∆ψ m and reduction of apoptosis that was followed (at 4–8 h) by an accelerated collapse of ∆ψ m and cell death. In contrast, treatment with NCX‐4016, but not with aspirin or a non‐NO‐releasing analogue of NCX‐4016, protected HUVEC against the apoptotic actions of staurosporine for up to 8 h. Confocal microscopy demonstrated that although NCX4016 released NO in subcellular compartments, DETA‐NO caused a generalized increase in cytosolic fluorescence. Exposure to DETA‐NO resulted in a rapid and profound inhibition of cell respiration (78.3 ± 6.4%), whereas NCX‐4016 caused a less pronounced reduction in oxygen consumption (43.5 ± 5.3%). Staurosporine caused a time‐dependent activation of proapoptotic caspases. NCX‐4016 prevented this activation, whereas DETA‐NO failed to inhibit caspase activity. In contrast to DETA‐NO, NCX‐4016 did not increase mitochondrial oxidative stress. These data demonstrated that NCX‐4016 conveys NO directly inside endothelial cells and modulates mitochondrial function.

This publication has 32 references indexed in Scilit: