Mild hypothermia shows protective effects on patients with brain damage and cardiac arrest. To elucidate the molecular mechanisms underlying these effects, we analyzed the effects of low culture temperature (32 °C) and cold-inducible RNA-binding protein (Cirp) expression on apoptosis in vitro. In BALB/3T3 cells treated with tumor necrosis factor (TNF)-α and cycloheximide, the down-shift in temperature from 37 °C to 32 °C increased the expression of Cirp and suppressed the apoptosis. Activation of caspase-8 was suppressed, and the level of phosphorylated extracellular signal-regulated kinase (ERK) was increased. Transduction of Cirp into the Cirp-deficient mouse fibroblasts increased the level of phosphorylated ERK and suppressed the TNF-α-induced apoptosis both at 37 °C and 32 °C. The ERK-specific inhibitor PD98059 decreased the cytoprotective effect of Cirp as well as that of low culture temperature. These data suggest that mild hypothermia protects cells from TNF-α-induced apoptosis, at least partly, via induction of Cirp, and that Cirp protects cells by activating the ERK pathway.
|ジャーナル||Biochimica et Biophysica Acta - Molecular Cell Research|
|出版ステータス||Published - 2006 3|
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