Organ specific alteration in caspase expression and STK3 proteolysis during the aging process

Publication date: Available online 15 July 2016
Source:Neurobiology of Aging
Author(s): Mélissa Lessard-Beaudoin, Mélissa Laroche, Amal Loudghi, Marie-Josée Demers, Jean-Bernard Denault, Guillaume Grenier, Sean-Patrick Riechers, Erich E. Wanker, Rona K. Graham
Caspases and their substrates are key mediators of apoptosis and strongly implicated in various physiological processes. As the STK family is involved in apoptosis, and STK3 is a recently identified caspase-6 substrate, we assessed the expression and cleavage of STK3 in murine peripheral organs and brain regions during the aging process. We also assessed caspase-3, -6, -7 and -8 expression and activity in order to delineate potential mechanism(s) underlying the generation of the STK3 fragments observed, and their relation to the apoptotic pathway. We demonstrate for the first time the cleavage of STK3 by caspase-7 and show that STK3 protein levels globally increase throughout the organism with age. In contrast, caspase-3, -6, -7 and -8 expression and activity vary significantly amongst the different organs analyzed suggesting differential effects of aging on the apoptotic mechanism and/or non-apoptotic functions of caspases throughout the organism. These results further our understanding of the role of caspases and their substrates in the normal aging process and highlight a potential role for STK3 in neurodegeneration.



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