Circadian/HSR systems are indispensable for cOS-evoked responses.

<p>(A) HSF1 or BMAL1 deficiency abolishes cOS-synchronized circadian Per2 rhythms and HSE-driven acute surge. Wild-type (Wild) (a,d), BMAL1^−/− (b,d), and HSF1^−/− (c,d) MEFs transfected with the expression vector for Per2-Luc and HSE-SLR were OS-pulsed. Acute (a-c) and circadian (d) profiles were monitored by real-time bioluminescence assay. Relative (RLU) or normalized (deviation from moving average) profiles are shown (n = 4). (B) Each relative cell survival score 1 week after H₂O₂ treatment is shown. The score ++++ indicates 90–100% viable (negative control level), + indicates 25–50% viable, − indicates less than 25% viable (in this case, less than 5% viable). Annexin V/PI-FACS at 12 h post cOS-pulse reveals drastic apoptosis of BMAL1^−/− and HSF1^−/− MEFs in contrast to WT.