Peng Ruiyun

PI3K Activates NF-κB Signal Pathway Which Prevents IEC-6 Cells from Neutron Irradiation

Neutrons are high LET rays. It damages the bodies more seriously than γ rays. Intestinal epithelial cells are very sensitive to neutron irradiation. While by far, there are no papers concerning PI3K regulation of NF-κB signal pathway and its effects in the intestinal epithelial cells damaged by neutron irradiation. To explore the change of nuclear factor-kappa B (NF-κB) pathway in intestinal epithelial cell No.6 (IEC-6) cell line induced by fission neutron irradiation and the regulation of PI3K, we set up IEC-6 cell lines model by subculturing. Three groups of IEC-6 were given: control group, neutron irradiation group, LY294002 treatment and neutron irradiation group. Except the control group, the other groups were homogeneously irradiated by 4 Gy fission neutrons. The LY294002 treatment group cells were given LY294002 before 24 h of neutron irradiation. At 6 h and 24 h after neutron irradiation of 4 Gy, the proliferation ability of the IEC-6 cells was assayed by MTT colorimetry, the apoptosis and necrosis rates of the IEC-6 cells were assayed by flow cytometry (FCM), and changes of NF-κB (p65), the inhibitor of kappa Bα (IκBα) and IκB kinase β (IKKβ) were assayed by Western blotting. We quantitatively analyzed the results by means of image analysis. At 6 h and 24 h after neutron irradiation of 4 Gy, their proliferation ability decreased and lots of apoptosis and necrosis IEC-6 cells were found; the changes of NF-κB and IKKβ in IEC-6 cells were decreased and that of IκBα increased. The injuries of LY294002 treatment and neutron irradiation group were more serious than the control and neutron irradiation group. We found that IEC-6 cells were obviously damaged and induced serious apoptosis and necrosis by neutron irradiation of 4 Gy. The NF-κB pathway in IEC-6 cells was activated by neutron irradiation which can protect IEC-6 against injury caused by neutron irradiation. PI3K can activate NF-κB pathway which protects IEC-6 cells from being damaged by neutrons.

Administration of Recombinant Human Thrombopoietin Soon after Irradiation Promotes Survival and Stimulates Hematopoietic Recovery in a Nonhuman Primate Model of Radiation-Induced Severe Acute Radiation Syndrome

Accidental or intentional irradiation causes incidents involving acute radiation syndrome (ARS) victims. Thus, it is urgent to search for effective radioprotectors with no or low toxicity. Recombinant human thrombopoietin (rhTPO) is a megakaryocyte colony-stimulating factor. We have demonstrated previously that early administration of rhTPO soon after irradiation promotes survival of lethal dose irradiated mice. To evaluate the therapeutic effect of rhTPO short-term injection soon after radiation in nonhuman primates exposed to a high dose of gamma ray, rhesus monkeys received subcutaneously of early rhTPO 10 μg/kg injection at 0.5 and 24 h after or WR2721 30 mg/kg intramuscularly administration at 0.5 h before total body irradiated (TBI) with a 7 Gy gamma dose. Survival was monitored and hematopoiesis was evaluated at 40 d following early treatment. rhTPO short-term early injection (0.5 and 24 h) after 7 Gy TBI induced 100.0% survival versus 33.3% in irradiated controls, while 83.3% in WR2721 protected monkeys. rhTPO early treatment significantly promoted hematopoiesis recovery and apparently improved the quality of life, and additionally simplified supportive care in ARS rhesus monkeys. According to the survival and hematopoiesis of irradiated nonhuman primates, radioprotection of rhTPO short-term injection soon after TBI is better than WR2721 administration at 0.5 h before TBI. Thus short-term injection of rhTPO soon after irradiation might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims.