Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial CellsLovro Žiberna
, Mitja Martelanc
, Mladen Franko
, Sabina Passamonti
, 2016, original scientific article
Abstract: Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with
cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular
diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships.
Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric
detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To
confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a
high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass
spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9–1.5
pmol mg−1 protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular
bilirubin (3–5 pmol mg−1 protein) could be modulated by either extracellular bilirubin uptake, or by
up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis.
Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in
the range of reported values of free serum bilirubin (8.5–13.1 nM). Biliverdin showed similar antioxidant
properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and
may thus be a dynamic factor of the endothelial function.
Found in: osebi
Keywords: Antioxidants, bilirubin, endothelial cells
Published: 07.07.2016; Views: 3419; Downloads: 336
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