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

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 degreesC. We then show that heat treatment at 42 degreesC is able to trigger circadian oscillation of clock gene expression in NIH3T3 cells. This 42 degreesC 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.