Age dependent impact of LMP polymorphisms on TNFα-induced apoptosis in human peripheral blood mononuclear cells

M. Mishto, M. Bonafè, S. Salvioli, F. Olivieri, C. Franceschi

Research output: Contribution to journalArticle

Abstract

As a consequence of inflammatory stimuli (such as TNFα and IFNγ), some constitutive subunits of the proteasome, the principal mediator of nonlysosomal protein degradation, are replaced with other subunits, the large multifunctional proteases LMP2 and LMP7, thus originating the immunoproteasome. An age-related alteration of proteasome activity and susceptibility to TNFα-induced apoptosis, in which LMP2 and the nuclear factor (NF)-κB activation play an important role has been recently reported. In this paper, we investigated the possible influence of two LMP2 and LMP7 polymorphisms on susceptibility to TNFα-induced apoptosis. Our data show that an increase in susceptibility to TNFα-induced apoptosis is evident in long-lived people (aged > 88 years) in comparison to young individuals. Moreover, the modulation of LMP2 codon 60 polymorphism on TNFα-induced apoptosis is evident in long-lived subjects. Genotyping of 311 young people and 157 nonagenarians and centenarians revealed no changes in LMP2 codon 60 genotype frequency distribution. No correlation with TNFα-induced apoptosis and no difference in frequency between young people and nonagenarians/centenarians was observed when the LMP7 nucleotide 145 polymorphism was studied.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalExperimental Gerontology
Volume37
Issue number2-3
DOIs
Publication statusPublished - Jan 3 2002

Keywords

  • Aging
  • Apoptosis
  • Large multifunctional protease polymorphism
  • Nuclear factor-κB
  • Proteasome
  • Tumor necrosis factorα

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)

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