RESUMO
Altered structure, and hence function, of cellular macromolecules caused by oxidation can contribute to loss of physiological function with age. Here, we tested whether the lifespan of bats, which generally live far longer than predicted by their size, could be explained by reduced protein damage relative to short-lived mice. We show significantly lower protein oxidation (carbonylation) in Mexican free-tailed bats (Tadarida brasiliensis) relative to mice, and a trend for lower oxidation in samples from cave myotis bats (Myotis velifer) relative to mice. Both species of bat show in vivo and in vitro resistance to protein oxidation under conditions of acute oxidative stress. These bat species also show low levels of protein ubiquitination in total protein lysates along with reduced proteasome activity, suggesting diminished protein damage and removal in bats. Lastly, we show that bat-derived protein fractions are resistant to urea-induced protein unfolding relative to the level of unfolding detected in fractions from mice. Together, these data suggest that long lifespan in some bat species might be regulated by very efficient maintenance of protein homeostasis.
Assuntos
Homeostase , Longevidade , Proteínas/metabolismo , Animais , Quirópteros , Oxirredução , Estresse Oxidativo , Complexo de Endopeptidases do Proteassoma/metabolismo , Desnaturação Proteica , Especificidade da Espécie , UbiquitinaçãoRESUMO
MORF4-related gene on chromosome 15 (MRG15) is a core component of the NuA4/Tip60 histone acetyltransferase complex that modifies chromatin structure. We here demonstrate that Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit an impaired DNA-damage response post gamma irradiation, when compared to wild-type cells. Defects in DNA-repair and cell growth, and delayed recruitment of repair proteins to sites of damage were observed. Formation of phosphorylated H2AX and 53BP1 foci was delayed in Mrg15 mutant versus wild-type cells following irradiation. These data implicate a novel role for MRG15 in DNA-damage repair in mammalian cells.
Assuntos
Proteínas Cromossômicas não Histona/deficiência , Proteínas Cromossômicas não Histona/genética , Reparo do DNA , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/efeitos da radiação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Transativadores/deficiência , Transativadores/genética , Acetilação , Animais , Apoptose/efeitos da radiação , Núcleo Celular/metabolismo , Proliferação de Células/efeitos da radiação , Células Cultivadas , Proteínas Cromossômicas não Histona/metabolismo , Dano ao DNA , Proteínas de Ligação a DNA , Células-Tronco Embrionárias/citologia , Fibroblastos/citologia , Raios gama/efeitos adversos , Deleção de Genes , Heterozigoto , Histonas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Fosfoproteínas/metabolismo , Transativadores/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
A new longevity record has been established for a free-living bat-41 years for a male Brandt's bat, Myotis brandtii. The exceptional longevity of bats generally, and this species in particular, should make bats of special interest for researchers studying mechanisms of slow aging.
