Induction of P-glycoprotein overexpression in brain endothelial cells as a model to study blood-brain barrier efflux transport

• Published in: Frontiers in Drug Delivery Vol. 4
• Main Authors: Hathcock, Sarah F., Knight, Hallie E., Tong, Emma G., Meyer, Alexandra E., Mauser, Henry D., Vollmuth, Nadine, Kim, Brandon J.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 05-07-2024
• Subjects: blood-brain barrier; brain endothelial cells; drug screening; efflux transport; P-glycoprotein; puromycin
• ISSN: 2674-0850; 2674-0850
• DOI: 10.3389/fddev.2024.1433453

The blood-brain barrier (BBB) is comprised of specialized brain endothelial cells (BECs) that contribute to maintaining central nervous system (CNS) homeostasis. BECs possess properties such as an array of multi-drug efflux transporters that eject various drugs and toxins, preventing their entry into the CNS. Together, it is estimated that these efflux transporters can eject up to 98% of known xenobiotic compounds. P-glycoprotein (P-gp) is a promiscuous efflux transporter at the BBB and can efflux up to 90 various substrates, representing a major hurdle in CNS drug delivery for therapeutic interventions. This necessitates the study of P-gp to discover drugs that are non-substrates of P-gp as well as to identify novel P-gp inhibitors. Here we report the generation of P-gp overexpressing BECs under the endogenous promoter control that could be used in the screening of P-gp substrates. These cells could provide utility in the design of drugs or identification of novel inhibitors.