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Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin‐5 modulation
Author(s) -
Martin Tracey A.,
Das Tapas,
Mansel Robert E.,
Jiang Wen G.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20860
Subject(s) - occludin , tight junction , claudin , microbiology and biotechnology , paracellular transport , chemistry , endothelial stem cell , gamma linolenic acid , biology , biochemistry , permeability (electromagnetism) , polyunsaturated fatty acid , in vitro , fatty acid , membrane
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 (17β‐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 17β‐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 17β‐estradiol in these cells. J. Cell. Biochem. 98: 1308–1319, 2006. © 2006 Wiley‐Liss, Inc.