Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation.
Aging (Albany NY)
; 3(8): 794-802, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21937766
ABSTRACT
The Intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) are rhythmic and controlled by the circadian clock. However, whether NAD(+) oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD(+) hydrolase CD38. We found that rhythmicity of NAD(+) was altered in the CD38-deficient mice. The high, chronic levels of NAD(+) results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD(+) levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD(+) levels influence the circadian clock.
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Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
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Glicoproteínas de Membrana
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Regulação da Expressão Gênica
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Ritmo Circadiano
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ADP-Ribosil Ciclase 1
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NAD
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article