Effects of ischemia and H2O2 on the cold stress protein CIRP expression in rat neuronal cells

Expression of CIRP (cold-inducible RNA-binding protein) is inducible at 32°C in cultured fibroblasts. Because ischemia is known to induce expression of heat shock proteins, its effect on the CIRP expression was examined using the rat transient forebrain ischemia model. The isolated rat CIRP cDNA encoded amino acids 100% identical in its sequence to mouse CIRP. Northern blot analysis revealed that the CIRP transcripts were ubiquitously expressed in various tissues. In situ hybridization histochemistry of normal rat brain revealed the expression of CIRP in neurons in the hippocampus and the cerebral cortex among others. In the hippocampus of postischemic rats, CIRP mRNA level decreased from 3–6 h after the onset of reperfusion, while it did not change in the cerebral cortex. When PC12 pheochromocytoma cells were cultured at 32°C, the CIRP mRNA level was increased. The presence of H2O2 in the culture media inhibited dose dependently this induction as well as constitutive expression, suggesting that the effect of brain ischemia on CIRP expression is related to generation of reactive oxygen species. Further studies are necessary to clarify the roles played by cold shock proteins in the hypothermic therapy of brain damages.