altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat改变肝脏蛋白酶体组成组件有助于长寿的老人裸鼢鼠增强蛋白酶体活动.pdfVIP

altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat改变肝脏蛋白酶体组成组件有助于长寿的老人裸鼢鼠增强蛋白酶体活动.pdf

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altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat改变肝脏蛋白酶体组成组件有助于长寿的老人裸鼢鼠增强蛋白酶体活动

Altered Composition of Liver Proteasome Assemblies Contributes to Enhanced Proteasome Activity in the Exceptionally Long-Lived Naked Mole-Rat Karl A. Rodriguez1,2, Yael H. Edrey1,2, Pawel Osmulski1,3, Maria Gaczynska1,3, Rochelle Buffenstein1,2,4* 1 Sam and Ann Barshop Institute for Aging and Longevity Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America, 2 Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America, 3 Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America, 4 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America Abstract The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was

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