BackgroundThe previous investigation demonstrated the radioprotective efficacy of peptides isolated from the venom of Buthus Martti Karsch. In this study, the effect of isolated scorpion venom peptide II (SVPII) on irradiated M-NFS-60 cells and mouse bone marrow mononuclear cells (BM-MNCs) was observed. The AlamarBlue cell viability assay, a colony-forming unit (CFU) assay, flow cytometry (FCM), immunofluorescence, and Western blotting were used to evaluate cell proliferation, cell cycle progression, and the expression of the IL-3 receptor (IL-3R) protein in non-irradiated and irradiated cells.ResultsProliferation of irradiated M-NFS-60 cells was significantly accelerated by SPVII, and this effect was further enhanced by co-application of IL-3. Similarly, SPVII increased the number of BM-MNC CFUs and this proliferative effect was greater in the presence of SVPII plus IL-3. In addition, SPVII significantly altered cell cycle progression; SVPII enhanced the fraction of unirradiated M-NFS-60 cells in S phase and the fraction of irradiated M-NFS-60 cells arrested in G2/M. The expression of IL-3R protein by unirradiated M-NFS-60 cells was enhanced significantly by SVPII, and SVPII-induced IL-3R overexpression was 10-fold greater in irradiated M-NFS-60 cells.ConclusionsThese results indicated the hematopoietic growth factor (HGF)-like effects of SVPII on irradiated cells, possibly mediated by upregulation of IL-3R.

Scorpion venom peptide B5 (SVP-B5) stimulates recovery of hematopoiesis after exposure to radiation. However, its radioprotective effects and mechanisms are still unclear. The aim of this study was to investigate the effects of SVP-B5 on hematopoietic recovery in mice after total body irradiation (TBI) at a dose of 7.5Gy and 6Gy and to explore the possible primary mechanisms. SVP-B5 at a dose of 2.63 μg/kg significantly reduced the mortality rate of mice after TBI (p < 0.05). It showed markedly protective effects against radiation injury. SVP-B5 also significantly increased the number of bone marrow nucleated cells (BMNCs) and increased the colony forming unit (CFU) number in irradiated mice, accelerated the post-irradiation recovery of peripheral blood leukocytes and platelets in mice. SVP-B5 treatment markedly reduced the Reactive Oxygen Species (ROS) levels in BMNCs after TBI, reduced γH2AX levels, and decreased the relative expression levels of p16 and p21 mRNA at day14 (d14) after irradiation. Our study indicated that SVP-B5 could partially mitigate radiation-induced DNA damage, enhance the post-radiation hematopoietic recovery, and improve the survival rate probably through the ROS-p16/p21 pathway.

Abstract. Previous studies have demonstrated the radioprotective efficacy of scorpion venom peptide, fraction II (SVPII) from the venom of Buthus martensii Karsch. In the present study, the SVP-B5 polypeptide, which is one of the active components of SVPII, was purified using a two-step chromatographic process. SVP-B5 significantly promoted the proliferation of irradiated M-NFS-60 mouse-derived myelocytic leukemia cells. In addition, SVP-B5 effectively and persistently promoted hematopoietic recovery and expansion of hematopoietic cells after irradiation as demonstrated by cobblestone area forming cell and long-term bone marrow culture assays. Treatment of M-NFS-60 cells with SVP-B5 upregulated the expression of interleukin 3 receptor and activated the Janus kinase-2/signal transducer and activator of transcription 5 signaling pathway. In conclusion, the present study demonstrated that SVP-B5 has growth factor-like properties and may be used as a therapeutic modality in the recovery of severe myelosuppression, which is a common side effect of radiotherapy.