Temperature compensation and temperature resetting of circadian rhythms in mammalian cultured fibroblasts

Abstract

Background: Circadian rhythms control many physiological processes. One of characteristic properties of circadian rhythms is insensitivity to temperature, called temperature compensation. Although this temperature-insensitive property has repeatedly been observed mainly in circadian output rhythms, temperature effect on autoregulatory feedback loops of clock gene expression, the rhythm-generating mechanisms, has not been fully investigated. Results: We show first that the circadian oscillation of clock gene expression in NIH3T3 fibroblasts, which is induced by TPA (12-O-tetradecanoylphorbol-13-acetate) treatment, is strongly temperature-compensated over the temperature range of 33-42 °C. We then show that heat treatment at 42 °C is able to trigger circadian oscillation of clock gene expression in NIH3T3 cells. This 42 °C heat treatment, unlike serum shock or TPA treatment, did not induce immediate expression of mPer1 mRNA, suggesting the existence of several different resetting mechanisms. Conclusions: This is the first demonstration of temperature compensation of the rhythm-generating core feedback loops of clock gene expression in mammalian cultured cells. It is possible that cells in the periphery could sense the change of ambient temperature as a resetting cue and that the whole organism thus could be entrained rapidly at dawn, in cooperation with the resetting mechanism by light.