Fig. 1.
Mechanisms of circadian rhythms. (A) Molecular mechanism: the circadian clock is composed of a primary negative feedback loop involving the genes Clock, Bmal1, Period homologue 1 (Per1), Per2, Cryptochrome 1 (Cry1), and Cry2. This clockwork is composed of a set of proteins that are synchronized by daylight (Per1, Per2) in the central nervous system and peripheral organs. Periods (Per) are nuclear proteins that belong to the so-called PAS domain superfamily and are cofactors of transcription. PAS stands for Period, Arnt, and Sim, three drosophila genes in which the PAS domain was discovered. Hypoxia-inducible factor 1α (Hif1a) that plays an important role in hypoxic and ischemic disease states also belong to this family of PAS-domain–positive proteins. The PAS domain has been described as a binding site to allow interactions between those proteins and to sense oxygen or light. (B) Correlation between infarct sizes (myocardial infarction [MI]) and cardiac Per2 levels. Per2 levels are regulated by daylight. Recent studies recognized a relation between daylight-elicited Per2 levels and the severity of myocardial ischemia. (C) Proposed cardioprotective mechanisms mediated by circadian regulators via daylight exposure. SCN = suprachisasmatic nuclei.