Age-related differences in the dynamics of hippocampal proteasome recovery

Authors

  • M. Paz Gavilán,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
    2. Centro Andaluz de Biología y Medicina Regenerativa (CABIMER), Sevilla, Spain
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  • Cristina Pintado,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
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  • Elena Gavilán,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
    2. Centro Andaluz de Biología y Medicina Regenerativa (CABIMER), Sevilla, Spain
    3. Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
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  • Luisa M. García-Cuervo,

    1. Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
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  • Angelica Castaño,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
    2. Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
    3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sevilla, Spain
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  • Rosa M. Ríos,

    1. Centro Andaluz de Biología y Medicina Regenerativa (CABIMER), Sevilla, Spain
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  • Diego Ruano

    Corresponding author
    1. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
    2. Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
    3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sevilla, Spain
    • Address correspondence and reprint requests to Dr Diego Ruano, Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Avd Manuel Siurot s/n, 41013-Sevilla, Spain. E-mail: ruano@us.es

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Abstract

Regulation of proteasome abundance to meet cell needs under stress conditions is critical for maintaining cellular homeostasis. However, the effects of aging on this homeostatic response remain unknown. In this report, we analyzed in young and aged rat hippocampus, the dynamics of proteasome recovery induced by proteasome stress. Proteasome inhibition in young rats leads to an early and coordinate transcriptional and translational up-regulation of both the catalytic subunits of constitutive proteasome and the proteasome maturation protein. By contrast, aged rats up-regulated the inducible catalytic subunits and showed a lower and shorter expression of proteasome maturation protein. This resulted in a faster recovery of proteasome activity in young rats. Importantly, proteasome inhibition highly affected pyramidal cells, leading to the accumulation of ubiquitinated proteins in perinuclear regions of aged, but not young pyramidal neurons. These data strongly suggest that age-dependent differences in proteasome level and composition could contribute to neurodegeneration induced by proteasome dysfunction in normal and pathological aging.

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