Cellular Models for Liver Toxicity: keeping track of time

Abstract

As a direct result of the composition of our solar system, life on earth is continuously exposed to temporal changes to the environment. Apart from annual, seasonal and lunar cycles, we experience 24-hour light/dark and temperature cycles, caused by the rotation of the earth around its own axis. To cope with these cyclic changes organisms have acquired an internal timing mechanism with a periodicity of approximately 24 hour (Edery, 2000). This circadian clock (Lat. circa = near, dies = day) is an anticipatory mechanism that allows an organism to adjust behavior, physiology and metabolism (e.g. body temperature, sleep-wake cycle, blood pressure and locomotor activity) to the specific needs at defined stages over the day (Lowrey & Takahashi, 2004; Reppert & Weaver, 2002). The importance of circadian clocks is well illustrated by the fact that they evolved multiple times during evolution and are present in almost all life forms on earth, ranging from single cellular organisms (e.g. bacteria) to multicellular organisms (e.g. plants and animals) (Bell-Pedersen et al., 2005; Dunlap, 1999). Circadian clock research has largely focused on a series of model organisms, notably the filamentous fungus Neurospora crassa, the plant Arabidopsis thaliana, the fruit fly Drosophila melanogaster, zebrafish, rodents, and humans (Dunlap, 1999; Kantermann et al., 2007). Circadian rhythms are defined as being endogenous, self-sustained, persisting in the absence of any environmental cues (such as the light/dark cycle) and their close approximation to the period of the earth’s rotation (Pittendrigh, 1960).