Intermittent hypoxia regulates RNA polymerase II in hippocampus and prefrontal cortex.
Neuroscience
; 158(4): 1436-45, 2009 Feb 18.
Article
en En
| MEDLINE
| ID: mdl-19095046
ABSTRACT
Intermittent hypoxia (IH) is a major pathological factor in the development of neural deficits associated with sleep-disordered breathing. Here we demonstrate that IH lasting 2 or 30 days, but not sustained hypoxia (SH) of the same duration, was accompanied by several posttranslational modifications of the large subunit of RNA polymerase II, Rpb1, including hydroxylation of proline 1465, phosphorylation of serine 5 residues within the C-terminal domain, and nondegradative ubiquitylation. These modifications were found to occur in two regions of the brain, hippocampal region CA1 and the prefrontal cortex, but not in neocortex, brainstem and CA3 region of hippocampus. We also found that mice exposed to 14 or 30 days of IH, but not SH, demonstrated cognitive deficits in behavioral assays. Furthermore, by using the pheochromocytoma-derived PC12 cell line, we showed that, under in vitro IH conditions, induction of Rpb1 hydroxylation, phosphorylation, and ubiquitylation required that the von Hippel-Lindau protein be present. We hypothesize that the observed modifications of Rpb1 participate in regulating the expression of genes involved in mediating cognitive deficits evoked by chronic IH.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Polimerasa II
/
Regulación de la Expresión Génica
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Corteza Prefrontal
/
Hipocampo
/
Hipoxia
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos