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Objective:To investigate the expression changes of lncRNAs and mRNAs in human umbilical vein endothelial cells(HUVEC) treated by tritiated water.Methods:HUVEC cells were divided into two groups, the control group cultured in DMEM medium, and the tritiated water exposure group cultured in a medium containing tritiated water with a final concentraion of 3.7×10 3 Bq/ml. After culture for 48 h, cells were collected for RNA extract.The differentially expressed lncRNAs and mRNAs were screened by high-through put chip technology and then analyzed. Results:Compared with the control group, 1 717 lncRNAs were significantly up-regulated and 3 994 lncRNAs significantly down-regulated, and 4 562 mRNAs were significantly up-regulated and 1 433 mRNAs down-regulated. Through co-expression analysis of differential mRNAs and lncRNAs, some key genes including SQSTM1, CXCL8, ITPR1, GADD45A, NF-kB1 and VDAC1 were obtained.Conclusions:Tritiated water exposure can induce multiple changes of mRNAs and lncRNAs in vascular endothelial cells, which may lead to toxic effects through signaling pathways including some key genes such as SQSTM1, CXCL8, and ITPR1.
ABSTRACT
Objective@#To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO).@*Methods@#Hippocampal neural cells from newborn Sprague-Dawley(SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20% of fetal bovine serum for 6 days, followed by subjection to tritiated water(HTO) at concentrations of 3.7×102, 3.7×103, 3.7×104, 3.7×105, 3.7×106 Bq/ml for 24 h, respectively. Western blot and RT-qPCR were used to determine the expression levels of F-actin, α-tubulin, tau, AP2, BDNF mRNA and Reelin mRNA. 16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/ each group). The tested rats were injected with body fluid of HTO (3.7×106 Bq/g) intraperitoneally, while the saline as the control. Morris water maze (MWM) was employed for the spatial learning and memory of rats.@*Results@#Compared to the control cells, HTO caused a significant downregulation of expressions of cytoskeletal proteins [F-actin (t=8.898-19.896, P<0.05), α-tubulin (t=3.261-7.900, P<0.05), tau (t=2.274-5.003, P<0.05), and MAP2 (t=2.274-5.003, P<0.05)] and mRNA of BDNF(t=3.580-19.792, P<0.05) and Reelin (t=3.240-39.692, P<0.05) in the tested neural cells in a dose-dependent manner. In addition, the escape latency of irradiated offsprings was significantly prolonged (t=-2.563, P<0.05), the time for offsprings to cross through target quadrant was markedly reduced (t=3.214, P<0.05), and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t=3.874, P<0.05) in the MWM trial.@*Conclusions@#The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction, which may shed a light on a mechanism of the radiation-induced brain impairment.
ABSTRACT
Objective To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO).Methods Hippocampal neural cells from newborn Sprague-Dawley (SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20％ of fetal bovine serum for 6 days,followed by subjection to tritiated water (HTO) at concentrations of 3.7× 102,3.7×103,3.7 × 104,3.7 × 105,3.7× 106 Bq/ml for 24 h,respectively.Western blot and RT-qPCR were used to determine the expression levels of F-actin,α-tubulin,tau,AP2,BDNF mRNA and Reelin mRNA.16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/ each group).The tested rats were injected with body fluid of HTO (3.7× 106 Bq/g) intraperitoneally,while the saline as the control.Morris water maze (MWM) was employed for the spatial learning and memory of rats.Results Compared to the control cells,HTO caused a significant downregulation of expressions of cytoskeletal proteins [F-actin (t =8.898-19.896,P＜ 0.05),α-tubulin (t=3.261-7.900,P＜0.05),tau (t=2.274-5.003,P＜0.05),and MAP2 (t=2.274-5.003,P＜0.05)] and mRNA of BDNF (t=3.580-19.792,P＜0.05) and Reelin (t=3.240-39.692,P＜0.05)in the tested neural cells in a dose-dependent manner.In addition,the escape latency of irradiated offsprings was significantly prolonged (t =-2.563,P＜0.05),the time for offsprings to cross through target quadrant was markedly reduced (t=3.214,P＜0.05),and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t =3.874,P＜0.05) in the MWM trial.Conclusions The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction,which may shed a light on a mechanism of the radiation-induced brain impairment.