Cold-Inducible RNA-Binding Protein Expression And Its Neuroprotective Effect In Rat Brain

Cold stress induces synthesis of several proteins, comprising an amino-terminal consensus sequence RNA-binding domain and a carboxyl-terminal glycine-rich domain. These proteins have been termed'cold inducible RNA-binding proteins' (CIRPs). CIRP has been shown to suppress progression of the mitotic cell cycle. Hypothermia has been demonstrated to display organ-protective effects in animals and humans, and has been widely used in the treatment of severe head trauma and heart surgery, as well as in the preservation of donor organs. Nevertheless, the precise mode of protective action in hypothermia remains unknown. Increased CIRP expression has been observed in many mammalian cell lines following decreased temperatures. CIRP expression pattern in different organs under hypothermic conditions in vivo, as well as the role that CIRP plays in hypothermic therapy, remains to be elucidated. For these reasons, the present study focused on CIRP mRNA expression in the rat brain, prior to and following hypothermic and ischemic treatment. And then, the relationship between CIRP mRNA level and energy metabolism was analyzed. Finally, Overexpression of CIRP on SHG-44 cells were established and how the overexpression of CIRP affecting some neuroprotective compounds was measured. The results demonstrated that the expression of CIRP mRNA in rat's brain increased significantly under the hypothermic conditions, and the higher expression appeared regional difference. CIRP increasing in the rat, in particular in the rat brain, paralleled the reduction in temperature. Hypothermia, however, didn't affect the CIRP mRNA expression in the heart and liver. There was an increasing intendancy of CIRP mRNA expression in the cortex when treated with hypothermia and cerebral ischemia during the 24h observation period and the degree of increasing was much more significant in the former group. When treated with cerebral ischemia after hypothermia, CIRP mRNA expression in the cortex had also a significant increasing tendency, but ischemia delayed the appearance of the increasing tendency. The values of CIRP mRNA expression and lactate, pyruvate concentration and phosphofrucokinase level in the cortex in the three groups were analyzed by linear correlation. The data didn't support any correlation between CIRP expression and energy metabolism, suggesting CIRP does not affect cerebral energy metabolism. Overexpression of CIRP induced increasing EGF mRNA expression on SHG-44 cells, demonstrating that CIRP may play a role in neuroprotection by upregulating EGF.