The activation of caspases represents a critical step in the pathways leading to the biochemical and morphological changes that underlie apoptosis. Multiple pathways leading to caspase activation appear to exist and vary depending on the death-inducing stimulus. We demonstrate that the activation of caspase-3, in Jurkat cells stimulated to undergo apoptosis by a Fas-independent pathway, is catalyzed by caspase-6. Caspase-6 was found to co-purify with caspase-3 as part of a multiprotein activation complex from extracts of camptothecin-treated Jurkat cells. A biochemical analysis of the protein constituents of the activation complex showed that Hsp60 was also present. Furthermore, an interaction between Hsp60 and caspase-3 could be demonstrated by co-immunoprecipitation experiments using HeLa as well as Jurkat cell extracts. Using a reconstituted in vitro system, Hsp60 was able to substantially accelerate the maturation of procaspase-3 by different upstream activator caspases and this effect was dependent on ATP hydrolysis. We propose that the ATP-dependent 'foldase' activity of Hsp60 improves the vulnerability of pro-caspase-3 to proteolytic maturation by upstream caspases and that this represents an important regulatory event in apoptotic cell death.
We report the first two Canadian cases of combined heart-liver transplantation (CHLT) carried out on complete cardio-pulmonary bypass (CPB) with full anticoagulation. CLINICAL FEATURES: Consent for disclosure of these cases was obtained from both patients. Patient 1 was a 53 yearold man with familial hypertrophic cardiomyopathy who developed cirrhosis secondary to right ventricular failure. His past medical history included atrial fibrillation with sino-atrial ablation and pacemaker placement. He had normal LV function with severe RV diastolic dysfunction and congestive heart failure (NYHA class IV). Patient 2 was a 57 year-old man with hypertrophic restrictive cardiomyopathy with reduced LV function of 25-30% (NYHA class III heart failure), congestive hepatitis with cirrhosis, atrial fibrillation, ICD, chronic renal failure and mild COPD. Both patients were taking coumadin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.