Proteasome inhibitors shorten replicative life span and induce a senescent-like phenotype of human fibroblasts

Journal of Cellular Physiology
Claudio TorresVincent J Cristofalo

Abstract

The proteasome constitutes the main non-lysosomal cellular protease activity, and plays a crucial role not only in the disposal of unwanted material, but also in the regulation of numerous cellular processes. Previously, we have reported that during the replicative senescence of WI-38 fibroblasts there is a significant impairment in proteasome activity, which probably has important implications in the control of MAPK signaling and cellular proliferation. In this study, we report the potential role of the proteasome in the generation of the senescent phenotype in WI-38 fibroblasts. Our results indicate that inhibition of proteasome activity leads to an impairment in cell proliferation, and a shortening of the life span. The results also indicate that inhibition of the proteasome in young cells induces a premature senescent-like phenotype, as indicated by the increase in senescence-associated beta-galactosidase (SA beta-gal) activity and the abundance of both p21 and collagenase mRNAs, as well as a decreased level of EPC-1 mRNA known markers of cellular senescence, not previously shown to depend on proteasome activity. Together, our results suggest a molecular mechanism for the lack of responsiveness of human cells to growth fact...Continue Reading

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Citations

May 8, 2007·Ontogenez·E E EgorovA V Zelenin
Jul 14, 2010·Experimental Cell Research·Alessandro BittoClaudio Torres
Nov 10, 2009·Mechanisms of Ageing and Development·Elizabeth CroweClaudio Torres
Sep 23, 2009·Experimental Cell Research·Kaoru TominagaOlivia M Pereira-Smith
May 2, 2008·The Journal of Investigative Dermatology·Ivan B WallPhil Stephens
Dec 31, 2010·The Journal of Investigative Dermatology·Rafał KoziełPidder Jansen-Dürr
Nov 3, 2007·Free Radical Biology & Medicine·Claudio A Torres, Viviana I Perez
Aug 8, 2007·Aging Cell·Vita A VernaceMaria E Figueiredo-Pereira
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Jun 6, 2008·Mechanisms of Ageing and Development·Feng LiJeffrey N Keller
May 4, 2017·Antioxidants & Redox Signaling·Luis Ángel Maciel-BarónMina Königsberg
Dec 9, 2014·Nature Communications·David VilchezAndrew Dillin
Jun 22, 2018·Annual Review of Biochemistry·Charisma EnamRichard G Gardner
Jan 27, 2019·Molecular Psychiatry·Madeline R Scott, James H Meador-Woodruff
Mar 1, 2019·Aging Cell·Justin Cohen, Claudio Torres
Oct 18, 2019·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yoshiyuki ArataShigeo Murata
Jan 29, 2019·Frontiers in Endocrinology·María Carolina BarbosaClaudio Marcelo Fader
Jan 14, 2021·Cellular and Molecular Life Sciences : CMLS·Camilla S A Davan-WettonTrinidad Montero-Melendez
Jan 13, 2021·Experimental Cell Research·Anatoly Meller, Reut Shalgi
Sep 20, 2007·Journal of Cell Science·Wilfried CondemineHugues de Thé

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