INIBIBB 05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
artículos
Título:
Selective vulnerability of neurons to acute toxicity following proteasome inhibitor treatment: Implications for oxidative stress and insolubility of newly synthesized proteins
Autor/es:
DASURI, KALAVATHI; EBENEZER, PHILIP J.; ZHANG, LE; FERNANDEZ-KIM, SUN OK; URANGA, ROMINA MARÍA; GAVILÁN, ELENA; DI BLASIO, ALESSIA; KELLER, JEFFREY N.
Revista:
FREE RADICAL BIOLOGY AND MEDICINE
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Año: 2010
ISSN:
0891-5849
Resumen:
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Maintaining protein homeostasis is vital to cell
viability, with numerous studies demonstrating a role for proteasome inhibition
occurring during the aging of a variety of tissues, and presumably contributing
to the disruption of cellular homeostasis during aging. In the present study we
sought to elucidate the differences between neurons and astrocytes in regards
to basal levels of protein synthesis, proteasome-mediated protein degradation,
and sensitivity to cytotoxicity following proteasome inhibitor treatment. In
these studies we demonstrate that neurons have an increased vulnerability, as
compared to astrocyte cultures, to proteasome inhibitor-induced cytotoxicity. No significant difference was observed between
these two cell types in regards to the basal rates of protein synthesis, or
basal rates of protein degradation, in the pool of short-lived proteins. Following
proteasome inhibitor treatment neuronal crude lysates were observed to undergo
greater increases in the levels of ubiquitinated and oxidized proteins, and
selectively exhibited increased levels of newly synthesized proteins
accumulating within the insoluble protein pool, as compared to astrocytes. Together, these data suggest a role for increased
oxidized proteins and sequestration of newly synthesized proteins to the
insoluble protein pool, as potential mediators of the selective neurotoxicity
following proteasome inhibitor treatment. The implications for neurons
exhibiting increased sensitivity to acute proteasome inhibitor exposure, and
the corresponding changes in protein homeostasis observed following proteasome
inhibition, are discussed in the context of both aging and age-related
disorders of the nervous system.
