Caveolae and the organization of carbohydrate metabolism in vascular smooth muscle

Autor: Christopher D. Hardin, Pamela G. Lloyd
Rok vydání: 2001
Předmět:
Zdroj: Journal of Cellular Biochemistry. 82:399-408
ISSN: 1097-4644
0730-2312
Popis: 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 β methyl-cyclodextrin (CD) and examined the metabolism of [2-13C]glucose (a glycolytic substrate) and [1-13C]fructose 1,6-bisphosphate (FBP, a gluconeogenic substrate in PCMV) using 13C nuclear magnetic resonance spectroscopy. Caveolar disruption reduced flux of [2-13C]glucose to [2-13C]lactate, suggesting that caveolar disruption partially disrupted the glycolytic pathway. Caveolae disruption may also have resulted in a breakdown of compartmentation, since conversion of [1-13C]FBP to [3-13C]lactate was increased by CD treatment. Alternatively, the increased [3-13C]lactate production may reflect changes in FBP uptake, since conversion of [1-13C]FBP to [3-13C]glucose was also elevated in CD-treated cells. Thus, a link between caveolar organization and metabolic organization may exist. J. Cell. Biochem. 82:399–408, 2001. © 2001 Wiley-Liss, Inc.
Databáze: OpenAIRE