title: Control of MCT1 function in cerebrovascular endothelial cells by intracellular pH.
abstract: Monocarboxylic Acid Transporter 1 (MCT1) is expressed on the plasma membrane of cerebrovascular endothelial cells where it is the only known facilitator of lactic acid transport across the blood brain barrier. During stroke, brain injury, and certain other brain pathologies, anaerobic glycolysis produces severe lactic acidosis of brain tissue leading to brain cell damage. Therefore, a better understanding of factors that control MCT1 function may be the key to better understanding the origins and treatment of pathological lactic acidosis. In this study, we characterized the effects of intracellular pH in controlling MCT1 function and showed that microtubule disruption targeted this mechanism in rat cerebrovascular endothelial cells. Acidic intracellular pH values were shown to strongly inhibit lactic acid transport into the cytoplasmic space, while alkalinization of the cytoplasm significantly enhanced this transport function. These results support a better understanding of how cerebrovascular endothelial MCT1 may contribute to the development of lactic acidosis in brain pathologies, and suggest targeting it as a novel therapy.
authors.affiliation: Colorado State University—Pueblo, Department of Biology, 2200 Bonforte Boulevard, Pueblo, CO 81001, USA. auhernik@hotmail.com
authors.forename: Amy L
authors.initials: AL
authors.lastname: Uhernik
authors.forename: Carrie
authors.initials: C
authors.lastname: Tucker
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Smith
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002460:Cell Line; D003078:Colchicine / Q000633:toxicity; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D042783:Endothelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D042541:Intracellular Space / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000473:pathology; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D051381:Rats; D027981:Symporters / Q000378:metabolism*; D050257:Tubulin Modulators / Q000633:toxicity; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D003078:Colchicine; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D050257:Tubulin Modulators; D000099233:Monocarboxylate Transport Protein 1