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Neurobiol Aging. 2016 Nov;47:50-62. doi: 10.1016/j.neurobiolaging.2016.07.003. Epub 2016 Jul 15.

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

Author information

1
Research Centre on Aging, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada; Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada.
2
Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada; CHUS Research Center, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada; Institut de Pharmacologie de Sherbrooke, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada.
3
CHUS Research Center, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada; Department of Orthopaedic Surgery, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada.
4
Max Delbrück Centrum für Molekulare Medizin, Berlin, Germany.
5
Research Centre on Aging, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada; Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Faculty of Medicine and Health Sciences, Quebec, Canada. Electronic address: Rona.Graham@USherbooke.ca.

Abstract

Caspases and their substrates are key mediators of apoptosis and strongly implicated in various physiological processes. As the serine/threonine kinase family is involved in apoptosis and serine/threonine kinase 3 (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 among the different organs analyzed suggesting differential effects of aging on the apoptotic mechanism and/or nonapoptotic 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.

KEYWORDS:

Aging; Apoptosis; Brain region; Caspases; Peripheral organs; Serine/threonine kinase 3

[Indexed for MEDLINE]

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