Andrea E Tóth1, András Tóth1, Fruzsina R Walter2, Lóránd Kiss2, Szilvia Veszelka2, Béla Ózsvári3, László G Puskás3, Markus M Heimesaat4, Shinya Dohgu5, Yasufumi Kataoka5, Gábor Rákhely1, Mária A Deli6. 1. Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary; Department of Biotechnology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary. 2. Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. 3. Avidin Ltd., Szeged, Hungary; Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. 4. Department of Microbiology and Hygiene, Charité-University Medicine Berlin, Berlin, Germany. 5. Department of Pharmaceutical Care and Health Sciences, Fukuoka University, Fukuoka, Japan. 6. Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. Electronic address: deli.maria@brc.mta.hu.
Abstract
BACKGROUND AND AIMS: Elevated levels of reactive carbonyl species such as methylglyoxal triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Carbonyl stress is implicated in conditions and diseases like aging, diabetes mellitus, Alzheimer's disease and cardiovascular diseases. Our aim was to examine the effects of methylglyoxal on human hCMEC/D3 brain endothelial cells and search for protective molecules to prevent endothelial damage. METHODS: Methylglyoxal-induced modification of albumin was tested in a cell-free assay. Endothelial cell viability was monitored by impedance measurement in real-time. The following compounds were tested in cell-free and viability assays: β-alanine, all-trans-retinoic acid, aminoguanidine, ascorbic acid, L-carnosine, GW-3333, indapamide, piracetam, γ-tocopherol, U0126, verapamil. Barrier function of brain endothelial monolayers was characterized by permeability measurements and visualized by immunohistochemistry for β-catenin. mRNA expression level of 60 selected blood-brain barrier-related genes in hCMEC/D3 cells was investigated by a custom Taqman gene array. RESULTS: Methylglyoxal treatment significantly elevated protein modification, exerted toxicity, reduced barrier integrity, increased permeability for markers FITC-dextran and albumin and caused higher production of reactive oxygen species in hCMEC/D3 endothelial cells. Changes in the mRNA expression of 30 genes coding tight junction proteins, transporters and enzymes were observed in methylglyoxal-treated hCMEC/D3 cells. From the tested 11 compounds only all-trans-retinoic acid, an antioxidant and antiglycation agent, U0126, a MAP/ERK kinase inhibitor and aminoguanidine attenuated methylglyoxal-induced damage in hCMEC/D3 cells. CONCLUSIONS: All-trans-retinoic acid and inhibition of the MAP/ERK signaling pathway may be protective in carbonyl stress induced brain endothelial damage.
BACKGROUND AND AIMS: Elevated levels of reactive carbonyl species such as methylglyoxal triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Carbonyl stress is implicated in conditions and diseases like aging, diabetes mellitus, Alzheimer's disease and cardiovascular diseases. Our aim was to examine the effects of methylglyoxal on human hCMEC/D3 brain endothelial cells and search for protective molecules to prevent endothelial damage. METHODS:Methylglyoxal-induced modification of albumin was tested in a cell-free assay. Endothelial cell viability was monitored by impedance measurement in real-time. The following compounds were tested in cell-free and viability assays: β-alanine, all-trans-retinoic acid, aminoguanidine, ascorbic acid, L-carnosine, GW-3333, indapamide, piracetam, γ-tocopherol, U0126, verapamil. Barrier function of brain endothelial monolayers was characterized by permeability measurements and visualized by immunohistochemistry for β-catenin. mRNA expression level of 60 selected blood-brain barrier-related genes in hCMEC/D3 cells was investigated by a custom Taqman gene array. RESULTS:Methylglyoxal treatment significantly elevated protein modification, exerted toxicity, reduced barrier integrity, increased permeability for markers FITC-dextran and albumin and caused higher production of reactive oxygen species in hCMEC/D3 endothelial cells. Changes in the mRNA expression of 30 genes coding tight junction proteins, transporters and enzymes were observed in methylglyoxal-treated hCMEC/D3 cells. From the tested 11 compounds only all-trans-retinoic acid, an antioxidant and antiglycation agent, U0126, a MAP/ERK kinase inhibitor and aminoguanidine attenuated methylglyoxal-induced damage in hCMEC/D3 cells. CONCLUSIONS:All-trans-retinoic acid and inhibition of the MAP/ERK signaling pathway may be protective in carbonyl stress induced brain endothelial damage.
Authors: Ryan B Griggs; Diogo F Santos; Don E Laird; Suzanne Doolen; Renee R Donahue; Caitlin R Wessel; Weisi Fu; Ghanshyam P Sinha; Pingyuan Wang; Jia Zhou; Sebastian Brings; Thomas Fleming; Peter P Nawroth; Keiichiro Susuki; Bradley K Taylor Journal: Neurobiol Dis Date: 2019-02-23 Impact factor: 5.996
Authors: Szilvia Veszelka; András Tóth; Fruzsina R Walter; Andrea E Tóth; Ilona Gróf; Mária Mészáros; Alexandra Bocsik; Éva Hellinger; Monika Vastag; Gábor Rákhely; Mária A Deli Journal: Front Mol Neurosci Date: 2018-05-22 Impact factor: 5.639
Authors: Mikhail V Samsonov; Asker Y Khapchaev; Alexander V Vorotnikov; Tatyana N Vlasik; Elena V Yanushevskaya; Maria V Sidorova; Evgeniy E Efremov; Vadim Z Lankin; Vladimir P Shirinsky Journal: Oxid Med Cell Longev Date: 2017-10-02 Impact factor: 6.543
Authors: Ali S Alqahtani; Wael M Abdel-Mageed; Abdelaaty A Shahat; Mohammad K Parvez; Mohammed S Al-Dosari; Ajamaluddin Malik; Maged S Abdel-Kader; Mansour S Alsaid Journal: J Food Drug Anal Date: 2019-03-17 Impact factor: 6.157