albumin - publications
The Effect of Cellular Senescence on the Albumin Permeability of Blood-Derived Endothelial Cells.
Am J Physiol Heart Circ Physiol. 2012 Sep 28;
Authors: Cheung TM, Ganatra MP, Peters EB, Truskey GA
In this study, we tested the hypotheses that endothelial cells derived from human umbilical cord blood (hCB-ECs) exhibited low permeability which increased as the hCB-ECs age and undergo senescence and that the change in permeability of hCB-ECs is due to changes in tight junction protein localization and the activity of Epac1. Albumin permeability across low passage hCB-EC monolayers on Transwell membranes was 10X lower than for human aortic endothelial cells (HAECs) (p<0.01), but similar to in vivo values in arteries. Expression of tight junction protein occludin and tyrosine phosphorylation of occludin were less in hCB-ECs than in HAECs (p<0.05). More hCB-ECs than HAECs underwent mitosis (p<0.01). The hCB-ECs that underwent >44 population doublings since isolation had a significantly higher permeability than hCB-ECs that underwent <31 population doublings (p<0.05). This age-related increase in hCB-EC permeability was associated with an increase in tyrosine phosphorylation of occludin (p<0.01); permeability and occludin phosphorylation were reduced by treatment with 2μM Resveratrol. Tyrosine phosphorylation of occludin and cell age influence the permeability of hCB-ECs, whereas levels of EC proliferation and expression of tight junction proteins do not explain differences between hCB-EC and HAEC permeability. The elevated permeability in late passage hCB-ECs was reduced by 25%-40% by elevation of membrane-associated cAMP and activation of the Epac1 pathway. Given the similarity to in vivo permeability to albumin and the high proliferation potential, hCB-ECs may be a suitable in vitro model to study transport-related pathologies and cell aging.
PMID: 23023872 [PubMed - as supplied by publisher]