1. Newborn- and Adult-Derived Brain Microvascular Endothelial Cells Show Age-Related Differences in Phenotype and Glutamate-Evoked Protease Release
- Author
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Séverine Launay, Stéphane Marret, Hélène Legros, Julie Catteau, Benoit D. Roussel, Denis Vivien, Philippe Leroux, Olivier Boyer, Vincent Laudenbach, Aurélie Marcou-Labarre, Carine Ali, and Sébastien Calbo
- Subjects
Monocarboxylic Acid Transporters ,Aging ,medicine.medical_specialty ,Glutamic Acid ,Receptors, N-Methyl-D-Aspartate ,Tissue Culture Techniques ,Mice ,Internal medicine ,medicine ,Animals ,Cell Shape ,Cells, Cultured ,Monocarboxylate transporter ,Symporters ,biology ,T-plasminogen activator ,Glutamate receptor ,Glucose transporter ,Brain ,Endothelial Cells ,Endothelial stem cell ,Protein Subunits ,Phenotype ,Endocrinology ,Animals, Newborn ,Excitatory Amino Acid Transporter 2 ,Gene Expression Regulation ,Matrix Metalloproteinase 9 ,Neurology ,Microvessels ,cardiovascular system ,biology.protein ,Matrix Metalloproteinase 2 ,NMDA receptor ,GLUT1 ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Plasminogen activator ,Biomarkers - Abstract
Few data are available on the involvement of brain microvascular endothelial cells (BMECs) in excitotoxic neonatal brain lesions. Therefore, we developed an original approach for investigating mouse-derived BMECs in vitro. We hypothesized that newborn and adult BMEC cultures would show age-related differences in phenotype and sensitivity to glutamate. Expression of the monocarboxylate transporter, MCT1, was higher in neonatal than in adult BMECs, whereas expression of the glucose transporter, GLUT1, was higher in adult than in neonatal BMECs that overexpressed the N-methyl-D-aspartate receptor NR1 subunit (NMDAR1) compared with adult BMECs. The ability of neonatal and adult BMECs to be activated by glutamate was confirmed through intracellular calcium ([Ca2+]i) recording. The glutamate-induced [Ca2+]i increase was blocked by the selective NMDAR antagonist, MK-801. Significant glutamate-evoked concentration-dependent release of tissue-type plasminogen activator (t-PA) and matrix metalloproteinases (MMPs) activities was found in supernatants of neonatal, but not in adult BMECs. The glutamate-mediated release of t-PA, MMP-2, and MMP-9 proteolytic activities in neonatal BMECs was blocked by MK-801. Conceivably, this protease release from neonatal BMECs may participate in neonatal brain lesions.
- Published
- 2009