ABSTRACT
We have reviewed the transcriptional regulation of the CYP1A1 gene, which encodes the cytochrome P450IA1 enzyme. TCDD induces CYP1A1 transcription via a receptor- and enhancer-dependent mechanism that involves multiple protein-DNA interactions. The system provides an example of enzyme regulation at the level of gene transcription.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Gene Expression Regulation, Enzymologic/drug effects , Polychlorinated Dibenzodioxins/pharmacology , Receptors, Drug/physiology , Transcription, Genetic/drug effects , Animals , Aryl Hydrocarbon Hydroxylases/biosynthesis , Cell Line , Chromatin/drug effects , Chromatin/physiology , Enhancer Elements, Genetic/drug effects , Enzyme Induction , Liver Neoplasms, Experimental , Mice , Receptors, Aryl Hydrocarbon , Receptors, Drug/drug effectsABSTRACT
The eyes of several marine molluscs contain circadian pacemakers. The ocular pacemakers of one mollusc, Bulla gouldiana, are mutually coupled, and this coupling can be demonstrated in vitro. Induced phase separations between the two ocular pacemakers are reduced if the pacemakers are allowed to interact. The interaction between the pacemakers is mediated by the exchange of optic nerve impulses from eye to eye. In contrast, in vivo studies with another mollusc, Aplysia californica, have revealed that this snail's pacemakers are not strongly coupled. We have now determined in Bursatella leachi plei, an Opisthobranch closely related to A. californica, that the ocular pacemakers are mutually coupled. By virtue of the interaction between the pacemakers of B. leachi plei, the period of the ocular rhythm is increased by 1.5 h. In addition, eyes that remain attached to the nervous system show an increase in the sustainability of the free-running rhythm compared with isolated eyes. The increase in sustainability however, is due to the effects of attachment to the cerebral ganglion, and not the contralateral eye, since most single eyes attached to the brain show sustained, short-period rhythms. Thus, two properties of a circadian system, the pacemaker period and pacemaker sustainability, may be influenced by separate physiological mechanisms. We also confirm, using our in vitro techniques, the lack of strong coupling between the ocular pacemakers of A. californica.
Subject(s)
Aplysia/physiology , Circadian Rhythm , Mollusca/physiology , Animals , Ocular Physiological Phenomena , Optic Nerve/physiology , Species SpecificityABSTRACT
The eyes of Bulla gouldiana, a marine snail, contain circadian oscillators that are coupled to each other. Obvious candidates for the coupling signals are the optic nerve compound action potentials (CAPs) that express the circadian rhythm and lead to efferent impulses in the contralateral optic nerve. In the present experiments, the role of the CAPs as coupling signals was evaluated. We found that, following desynchronization of the two ocular oscillators by phase-delaying one eye with manganese, subsequent phase shifts in the initially unshifted ocular rhythm only occurred during the time that efferent optic nerve signals were present. In addition, in the absence of ocular desynchrony, phase shifts of the ocular rhythm could still be effected by activation of the efferent pathway. The influence of efferent impulses on identified retinal cells was also evaluated. No effect of efferent signals on receptor layer cells was detected, while it was found that efferent impulses generated depolarizations in basal retinal neurons (BRNs), the putative circadian oscillator cells. Depolarization of the BRNs has been shown previously to be involved in the light entrainment pathway. Depolarization appears to be similarly involved in the coupling pathway, since membrane depolarizations that mimicked the efferent-induced postsynaptic potentials likewise generated phase shifts of the ocular rhythm.
