Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin-5 modulation.
Tight junctions (TJs) in endothelial cells act as cell-cell adhesion structures, governing paracellular permeability (PCP). Disruption can lead to leaky vascular bed and potentially to oedema and swelling of tissues, the aetiology of mastalgia. These changes may also cause vascular spread of cancer cells. This study aimed to determine whether the function of TJs in endothelial cells can be strengthened by gamma linolenic acid (GLA), selenium (Se) and iodine (I) in the presence of 17beta-estradiol (17beta-estradiol), which causes leakage of endothelial cells by disruption of TJs in endothelium. GLA, I, and Se individually increased transendothelial resistance. The combination of all three agents also had a significant effect on TER. Addition of GLA/Se/I reduced PCP of the endothelial cells. Treatment with GLA/Se/I reversed the effect of 17beta-estradiol in reducing TER and increasing PCP. Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h there was increasing relocation to endothelial cell-cell junctions of the TJ proteins Claudin-5, Occludin, and ZO-1. Interestingly, this relocation was particularly evident with treatments containing I when probing with Claudin-5 and those containing Se for Occludin. There was a small increase in overall protein levels when examined by Western blotting after treatment with GLA/Se/I when probed with Claudin-5 and Occludin. We report that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells, by way of regulating the distribution of Claudin-5, Occludin, and ZO-1. Interestingly, this combination was also able to completely reverse the effect of 17beta-estradiol in these cells.
Martin
Tracey A
TA
Department of Surgery, Metastasis & Angiogenesis Research Group, Wales College of Medicine, Cardiff University, Heath Park, Cardiff, UK. Martinta1@cf.ac.uk
Das
Tapas
T
Mansel
Robert E
RE
Jiang
Wen G
WG
D000975:Antioxidants / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D062507:Claudin-5; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007455:Iodine / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism*; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D000975:Antioxidants; C107466:CLDN5 protein, human; D062507:Claudin-5; D008565:Membrane Proteins; D017965:gamma-Linolenic Acid; D007455:Iodine; D012643:Selenium