Thiol protease-thiol protease inhibitor imbalance in cardiac tissue of ageing cardiomyopathic hamsters.
In cardiomyopathic hamsters myofibrillar lesions and loss of muscle specific proteins occur in the heart early in life, and it has been suggested that intracellular proteases are involved in the process of muscle necrosis. In the age-dependent study reported here, we observed that cardiac tissue of dystrophic hamsters contains 30-100% more thiol protease activity than normal hamsters, with the greatest differences found in hearts of older animals. As well, the ratio of thiol protease activity in dystrophic hearts compared to normal hearts increases by 1.5-fold and 2.7-fold, respectively in the lysosomal and non-lysosomal fractions between 1.4 and 14 months of age. Cathepsin B accounted for over 90% of the thiol protease activity in the lysosomal fraction of both normal and dystrophic hamster hearts. In contrast, cardiac tissue of 3 to 14 month old dystrophic hamsters contains 20-45% less thiol protease inhibitor activity than hearts from age-matched normal hamsters. These results demonstrate that at an early age (1.4 to 3 months) an imbalance occurs between the thiol protease activity and thiol protease inhibitor content of cardiac tissue of dystrophic hamsters, which becomes more severe in older animals and associated with progressive myofibrillar lesions and tissue necrosis.
Warner
A H
AH
Department of Biological Sciences, University of Windsor, Ontario, Canada.
Ryan
M A
MA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases