title: Caveolar compartmentation of caspase-3 in cardiac endothelial cells.
abstract: Endothelial cell apoptosis is intimately involved in the balance between blood vessel growth and regression and is promoted by numerous stimuli including angiostatin and endostatin, reactive oxygen species (ROS) released during inflammatory processes, and chronic use of drugs of abuse such as cocaine. Apoptosis is characterized by many biological signalling events, including the activation of caspases. Caveolar domains have been hypothesized to mediate apoptotic signalling. We have addressed this hypothesis in cardiac endothelial cells and here we show that caspase-3 proenzyme (32 kDa) and its activated counterpart (17 kDa) co-purify with low-density, caveolin-enriched microdomains and that caspase-3 can be localized with caveolae in intact cells using fluorescent microscopy. Disruption of caveolae results in temporal and spatial changes in enzyme activity. While caspase-3 has been associated with mitochondrial, cytosolic, and high-density regions, the co-purification of activated caspase-3 and caveolar domains reported here suggests the possibility that sarcolemmal caspase-3 may be targeted to plasma-membrane associated substrates.
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, 1664 North Virginia Street, Reno, NV 89557-0046, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Oxhorn
authors.forename: Iain L O
authors.initials: IL
authors.lastname: Buxton
mesh_terms: D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism; D021941:Caveolae / Q000737:chemistry / Q000201:enzymology*; D051242:Caveolin 1; D022461:Caveolins / Q000032:analysis; D002451:Cell Compartmentation; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology*; D006168:Guinea Pigs; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology*
chemical_list: D051242:Caveolin 1; D022461:Caveolins; D002784:Cholesterol; D053148:Caspase 3; D020169:Caspases