ArticleFluids and barriers of the CNS2022
Hypoxia increases expression of selected blood-brain barrier transporters GLUT-1, P-gp, SLC7A5 and TFRC, while maintaining barrier integrity, in brain capillary endothelial monolayers.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Luteolin Attenuates Hypoxia-Induced Ferroptosis in Human Brain Microvascular Endothelial Cells Through Modulation of the PPARγ/FABP5/ALOX15 Signaling Pathway.Biomedicines · 2026Article
- In-Outside Hypoxia Remodeling Strategy Triggers Ferroptosis to Boost TACE Therapy in Hepatocellular Carcinoma.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Review
- Functional impact of high-altitude hypoxia on central nervous system drug transport: integrated analysis of blood-brain barrier permeability, drug transporter/enzyme expression, and pharmacokinetics.Fluids and barriers of the CNS · 2026Article
- Human brain pericytes protect the blood-brain barrier from triple-negative breast cancer cells while promoting tumor aggressiveness.Journal of cell communication and signaling · 2026Article
- IGF-mediated glucose signalling is retained in adult naked mole-rats.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Molecular Mechanisms of Juvenile Nasopharyngeal Angiofibroma: A Narrative Review.Current oncology (Toronto, Ont.) · 2026Review
- Oxytocin supports the barrier integrity of brain endothelial cells via oxytocin receptors.Journal of neuroendocrinology · 2026Article
- Article
- Mild chronic hypoxia and the brain: an ambiguous relationship.Journal of neuroinflammation · 2026Review
- Mitochondrial control of blood-brain barrier homeostasis in neuroinflammatory psychiatric disorders.Frontiers in molecular neuroscience · 2026Review
- GLUT1 and GLUT3 in brain glucose metabolism: mechanisms, regulation, and implications for metabolic disorders.Metabolic brain disease · 2025Review
- Marker-independent vibrational spectroscopy imaging recognizes the hypoxia effect in the human brain endothelium.Scientific reports · 2025Article
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress.Materials today. Bio · 2025Article
- Proteome profile differences among human, monkey, and mouse brain microvessels and cultured brain microvascular endothelial cells.Fluids and barriers of the CNS · 2025Article
- Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction.International journal of molecular sciences · 2025Review
- The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential.Molecular neurobiology · 2025Review
- The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.Journal of clinical medicine · 2025Review
- Progress in Epigenetic Modification Regulating Drug Transporters in the Hypoxic Environment.Current drug delivery · 2025Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrain capillary endothelial cells (BCECs) experience hypoxic conditions during early brain development. The newly formed capillaries are tight and functional before astrocytes and pericytes join the capillaries and establish the neurovascular unit. Brain endothelial cell phenotype markers P-gp (ABCB1), LAT-1(SLC7A5), GLUT-1(SLC2A1), and TFR(TFRC) have all been described to be hypoxia sensitive. Therefore, we hypothesized that monolayers of BCECs, cultured under hypoxic conditions, would show an increase in LAT-1, GLUT-1 and TFR expression and display tight endothelial barriers. METHODS AND
resultsPrimary bovine BCECs were cultured under normoxic and hypoxic conditions. Chronic hypoxia induced HIF-1α stabilization and translocation to the nucleus, as judged by immunocytochemistry and confocal laser scanning imaging. Endothelial cell morphology, claudin-5 and ZO-1 localization and barrier integrity were unaffected by hypoxia, indicating that the tight junctions in the BBB model were not compromised. SLC7A5, SLC2A1, and TFRC-mRNA levels were increased in hypoxic cultures, while ABCB1 remained unchanged as shown by real-time qPCR. P-gp, TfR and GLUT-1 were found to be significantly increased at protein levels. An increase in uptake of [
conclusionsOur findings collectively suggest that hypoxic conditions increase some BBB transporters' expression via HIF-1α stabilization, without compromising monolayer integrity. This may in part explain why brain capillaries show early maturation, in terms of barrier tightness and protein expression, during embryogenesis, and provides a novel methodological tool for optimal brain endothelial culture.
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