title: Caveolae and the organization of carbohydrate metabolism in vascular smooth muscle.
abstract: We have previously found that glycolysis and gluconeogenesis occur in separate "compartments" of the VSM cell. These compartments may result from spatial separation of glycolytic and gluconeogenic enzymes (Lloyd and Hardin [1999] Am J Physiol Cell Physiol. 277:C1250-C1262). We have also found that an intact plasma membrane is essential for compartmentation to exist (Lloyd and Hardin [2000] Am J Physiol Cell Physiol. 278:C803-C811), suggesting that glycolysis and gluconeogenesis may be associated with distinct plasma membrane microdomains. Caveolae are one such microdomain, in which proteins of related function colocalize. Thus, we hypothesized that membrane-associated glycolysis occurs in association with caveolae, while gluconeogenesis is localized to non-caveolae domains. To test this hypothesis, we disrupted caveolae in vascular smooth muscle (VSM) of pig cerebral microvessels (PCMV) with beta methyl-cyclodextrin (CD) and examined the metabolism of [2-(13)C]glucose (a glycolytic substrate) and [1-(13)C]fructose 1,6-bisphosphate (FBP, a gluconeogenic substrate in PCMV) using (13)C nuclear magnetic resonance spectroscopy. Caveolar disruption reduced flux of [2-(13)C]glucose to [2-(13)C]lactate, suggesting that caveolar disruption partially disrupted the glycolytic pathway. Caveolae disruption may also have resulted in a breakdown of compartmentation, since conversion of [1-(13)C]FBP to [3-(13)C]lactate was increased by CD treatment. Alternatively, the increased [3-(13)C]lactate production may reflect changes in FBP uptake, since conversion of [1-(13)C]FBP to [3-(13)C]glucose was also elevated in CD-treated cells. Thus, a link between caveolar organization and metabolic organization may exist.
authors.affiliation: Department of Physiology, University of Missouri, Columbia, Missouri 65212, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Lloyd
authors.forename: C D
authors.initials: CD
authors.lastname: Hardin
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply; D050260:Carbohydrate Metabolism; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003505:Cyclodextrins / Q000494:pharmacology; D005635:Fructosediphosphates / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013552:Swine; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D005635:Fructosediphosphates; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D005947:Glucose; C029063:fructose-1,6-diphosphate