RESUMO
Circadian entrainment involves photic stimulation of the suprachiasmatic molecular oscillator, including activation of the ERK/MAP kinase, which is phosphorylated endogenously during the day and in response to light during the night. We aimed to disrupt the diurnal cycle of ERK phosphorylation by in vivo transfection of a constitutively active form of MEK, a MAPK kinase. This procedure did not affect normal circadian parameters, but completely inhibited light-induced phase advances. Therefore, circadian regulation of the ERK pathway is not essential for the normal mechanism of the biological clock, but it is fundamental as an interface with environmental entrainment by light.
Assuntos
Ritmo Circadiano/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Mesocricetus/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Núcleo Supraquiasmático/enzimologia , Núcleo Supraquiasmático/fisiologia , Animais , Cricetinae , Ativação Enzimática , Proteínas de Fluorescência Verde/metabolismo , Masculino , Atividade Motora/fisiologia , TransfecçãoRESUMO
Circadian rhythms are entrained by light and by several neurochemical stimuli. In hamsters housed in constant darkness, i.c.v. administration of nerve growth factor (NGF) at various times in their circadian cycle produced phase shifts of locomotor activity rhythms that were similar in direction and circadian timing to those produced by brief pulses of light. Moreover, the effect of NGF and light were not additive, indicating signalling points in common. These points include the immediate-early gene c-fos and ERK1/2, a component of the mitogen-activated protein kinases (MAPK) family. NGF activates c-FOS and ERK1/2-MAPK in the suprachiasmatic nuclei, the site of a circadian clock in mammals, when administered during the subjective night but not during the day. The effect of NGF on ERK1/2 activation was not inhibited by the administration of MK-801, a glutamate/NMDA receptor antagonist. These results suggest that NGF, acting through MAPK activation, plays a role in photic entrainment of the mammalian circadian clock.
Assuntos
Ritmo Circadiano/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator de Crescimento Neural/farmacologia , Núcleo Supraquiasmático/efeitos dos fármacos , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Western Blotting/métodos , Contagem de Células/métodos , Cricetinae , Maleato de Dizocilpina/farmacologia , Interações Medicamentosas , Ativação Enzimática/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Regulação da Expressão Gênica/efeitos da radiação , Imuno-Histoquímica/métodos , Luz , Masculino , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Atividade Motora/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Núcleo Supraquiasmático/metabolismo , Fatores de TempoRESUMO
Circadian rhythms are entrained by light-activated signal transduction pathways in the biological clock. Among these, circadian and photic control of mouse suprachiasmatic ERK MAP kinase activation has been reported. In this paper we extend these results to hamsters and to the two other major members of the MAPK family: JNK and p38. The three kinases are rhythmically phosphorylated under light-dark and constant conditions, with maximal values during the day or subjective day. Light pulses during the subjective night induce rapid activation of the three enzymes, suggesting that the three MAP kinases might be implicated in mammalian photic entrainment.
