Inflammation Modulates RLIP76/RALBP1 Electrophile-Glutathione Conjugate Transporter and Housekeeping Genes in Human Blood-Brain Barrier Endothelial Cells

作者: Barbara Bennani-Baiti , Stefan Toegel , Helmut Viernstein , Ernst Urban , Christian R. Noe

DOI: 10.1371/JOURNAL.PONE.0139101

关键词: Molecular biologyTumor necrosis factor alphaInflammationReference genesCell biologyCell typeHousekeeping geneBiologyRegulation of gene expressionGene expressionBlood–brain barrier

摘要: Endothelial cells are often present at inflammation sites. This is the case of endothelial blood-brain barrier (BBB) patients afflicted with neurodegenerative disorders such as Alzheimer's, Parkinson's, or multiple sclerosis, well in cases bacterial meningitis, trauma, tumor-associated ischemia. Inflammation a known modulator gene expression through activation transcription factors, mostly NF-κB. RLIP76 (a.k.a. RALBP1), an ATP-dependent transporter electrophile-glutathione conjugates, modulates BBB permeability regulation tight junction function, cell adhesion, and exocytosis. Genes pathways regulated by transcriptional targets tumor necrosis factor alpha (TNF-α) pro-inflammatory molecule, suggesting that may also be target. To assess effects TNF-α on RLIP76, we faced problem choosing reference genes impervious to TNF-α. Since were not human cells, subjected these TNF-α, measured quantitative RT-PCR housekeeping commonly used genes. We find most modulated, analysis several datasets metaanalysis more than 5000 tissue samples encompassing 300 types diseases show no single gene. Using three different algorithms, however, uncovered geneset for first time induced follows induction kinetics markers, can influence BBB. MRP1 ABCC1), another transporter, modulated same conditions, indicating general property glutathione transporters. The herein should aid future studies inflammatory conditions

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