共查询到18条相似文献,搜索用时 187 毫秒
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长链非编码RNA(lncRNAs)是一类新的功能分子,可通过影响基因转录、蛋白质翻译以及蛋白质稳定性等方式调节下游靶基因,在生长发育、免疫应答、代谢调控以及肿瘤形成等生物学事件中发挥重要作用。已有研究表明lncRNAs可以通过电离辐射诱导表达,并参与细胞对电离辐射的应答反应以及细胞损伤修复过程。通过对电离辐射相关lncRNAs的研究有助于加深对电离辐射损伤应答机制的认识和了解。笔者对lncRNAs的结构功能、调控靶基因方式以及对电离辐射相关lncRNAs的功能和作用方式进行综述。 相似文献
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目的 筛选与鉴定电离辐射损伤相关的内皮细胞基因。方法 利用mRNA差异显示技术,以正常人脐静脉内皮细胞(HUVEC)和电离辐射后的HUVEC为实验材料,筛选与^60Coγ电离辐射损伤相关的基因片段。结果 经测序和鉴定,发现基因KIAA0456的两个外显子STSs和GSSs,ARF3基因在辐射后的内皮细胞中表达增加。结论 内皮细胞由上述两基因介导的细胞分化,信号传导,细胞粘附及增殖功能在辐射后增强。 相似文献
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目的 探讨神经上皮细胞转化基因1(Net1)对细胞辐射敏感性的影响及相关的分子作用机制.方法 运用实时荧光定量PCR检测辐射后细胞中Net1基因表达水平的变化;采用RNAi干扰技术抑制细胞中Net1的表达,用克隆形成率分析细胞的辐射敏感性;利用免疫共沉淀技术发现Net1的结合蛋白.结果 电离辐射损伤后,细胞中的Net1 mRNA水平显著上升(t=-10.52,P<0.05);与对照组相比,siRNA沉默细胞中的Net1表达后明显增加了细胞的辐射敏感性(t=15.31、11.65,P<0.05);无论在正常状态下还是在细胞受到辐照后,Net1都能与非同源末端连接修复蛋白Ku70、Ku80和DNA-PKcs结合.结论 Net1对细胞的辐射防护作用可能是通过与非同源末端连接修复蛋白相互作用来调控辐射损伤修复实现的. 相似文献
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Purpose: While the effects of high doses of ionizing radiation (IR) are relatively well characterized, the molecular mechanisms underlying cellular responses to prolonged exposure to low doses of radiation remain largely under-investigated.Materials and methods: Here, we addressed the DNA damage and apoptotic response in the spleen tissue of C57BL/6 male mice after fractionated exposure to X-rays within the 0.1–0.5?Gy dose range.Results: The response to initial exposure to 0.1?Gy of IR was characterized by increased DNA damage and elevated levels of apoptosis. Subsequent exposures (cumulative doses of 0.2 and 0.3?Gy) resulted in adaptive response-like changes, represented as increased proliferation and apoptotic response. Cumulative doses of 0.4 and 0.5?Gy were characterized by accumulation of DNA damage and reactivation of apoptosis and apoptosis-related proteins. Additionally, spleen cells with irreversible damage caused by radiation can undergo apoptosis via activation of p38, which does not necessarily involve the Atm/p53 pathway.Conclusions: Fractionated exposure to low doses of X-rays resulted in accumulation of DNA damage in the murine spleen and induction of apoptotic response in p53/Atm-independent manner. Further studies are needed to understand the outcomes and molecular mechanisms underlying cellular responses and early induction of p38 in response to prolonged exposure to IR. 相似文献
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New rationales for using TGFbeta inhibitors in radiotherapy 总被引:1,自引:0,他引:1
Andarawewa KL Paupert J Pal A Barcellos-Hoff MH 《International journal of radiation biology》2007,83(11-12):803-811
PURPOSE: The first reports that ionizing radiation (IR) induces rapid and persistent activation of transforming growth factor beta1 (TGFbeta) were nearly two decades ago. Subsequent studies have shown that TGFbeta is a major mediator of cellular and tissue responses to IR and have revealed novel facets of its complex biology. RESULTS: We and others have recently shown that inhibition of production or signaling of TGFbeta in epithelial cells modulates radiosensitivity and impedes activation of the DNA damage response program. The primary transducer of cellular response to DNA damage caused by ionizing radiation is the nuclear protein kinase ataxia telangiectasia mutated, whose activity is severely compromised when TGFbeta is inhibited. Thus, in conjunction, with its well-recognized contribution to normal tissue fibrosis, the role of TGFbeta in the genotoxic stress program provides a previously unsuspected avenue to modulate radiotherapy. CONCLUSIONS: We hypothesize that identification of the circumstances and tumors in which TGFbeta manipulation enhances tumor cell radiosensitivity, while protecting normal tissues, could significantly increase therapeutic index. 相似文献
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Mamon HJ Dahlberg W Azzam EI Nagasawa H Muto MG Little JB 《International journal of radiation biology》2003,79(10):817-829
PURPOSE: The ataxia-telangiectasia mutated (ATM) gene encodes a protein kinase, the activation of which is an early event in the cellular response to ionizing radiation. One of the many substrates of ATM is BRCA1 (breast cancer 1, early onset gene), which has been associated with susceptibility to breast and ovarian cancer, and has been implicated in DNA repair processes. Various cellular responses to radiation were analysed in cells with mutations in ATM or BRCA1 in an attempt to clarify which effects of ATM can be mediated through BRCA1. MATERIALS AND METHODS: The response to radiation of cells with mutations in ATM or BRCA1 was examined, as were BRCA1-mutant tumour cells transfected with an exogenous wild-type BRCA1 allele. Assays included cell-survival curves, studies of potentially lethal damage repair, measurement of chromosomal aberrations and of G1 arrest, and Western blot analysis of lysates of irradiated cells to determine the phosphorylation of the product of the human Mdm2 gene (HDM2). RESULTS: Both ATM and BRCA1 mutations were associated with sensitivity to ionizing radiation, deficient repair of potentially lethal damage and markedly increased chromosomal aberrations. A BRCA1-mutated tumour cell line HCC1937, like ATM mutant cells, did not exhibit a normal G1 arrest but, unlike ATM mutant cells, did exhibit phosphorylation of HDM2. Expression of wild-type BRCA1 in HCC1937 cells partially restored radioresistance, restored repair of potentially lethal damage and markedly reduced radiation-induced chromosomal aberrations. G1 arrest, however, was not restored by expression of BRCA1. CONCLUSIONS: The results are consistent with a model in which ATM phosphorylation of BRCA1 regulates DNA repair functions, particularly those involved in potentially lethal damage repair and chromosomal integrity, but not other aspects of the cellular response to radiation such as G1 cell cycle arrest. To the authors' knowledge, this is the first demonstration of the ability of exogenously expressed BRCA1 to restore the ability to perform potentially lethal damage repair and maintain chromosomal integrity in irradiated cells. 相似文献
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Kumari L. Andarawewa Jenny Paupert Anupama Pal 《International journal of radiation biology》2013,89(11-12):803-811
Purpose: The first reports that ionizing radiation (IR) induces rapid and persistent activation of transforming growth factor β1 (TGFβ) were nearly two decades ago. Subsequent studies have shown that TGFβ is a major mediator of cellular and tissue responses to IR and have revealed novel facets of its complex biology.Results: We and others have recently shown that inhibition of production or signaling of TGFβ in epithelial cells modulates radiosensitivity and impedes activation of the DNA damage response program. The primary transducer of cellular response to DNA damage caused by ionizing radiation is the nuclear protein kinase ataxia telangiectasia mutated, whose activity is severely compromised when TGFβ is inhibited. Thus, in conjunction, with its well-recognized contribution to normal tissue fibrosis, the role of TGFβ in the genotoxic stress program provides a previously unsuspected avenue to modulate radiotherapy.Conclusions: We hypothesize that identification of the circumstances and tumors in which TGFβ manipulation enhances tumor cell radiosensitivity, while protecting normal tissues, could significantly increase therapeutic index. 相似文献
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H. J. Mamon W. Dahlberg E. I. Azzam H. Nagasawa M. G. Muto J. B. Little 《International journal of radiation biology》2013,89(10):817-829
Purpose: The ataxia‐telangiectasia mutated (ATM) gene encodes a protein kinase, the activation of which is an early event in the cellular response to ionizing radiation. One of the many substrates of ATM is BRCA1 (breast cancer 1, early onset gene), which has been associated with susceptibility to breast and ovarian cancer, and has been implicated in DNA repair processes. Various cellular responses to radiation were analysed in cells with mutations in ATM or BRCA1 in an attempt to clarify which effects of ATM can be mediated through BRCA1.Materials and methods: The response to radiation of cells with mutations in ATM or BRCA1 was examined, as were BRCA1‐mutant tumour cells transfected with an exogenous wild‐type BRCA1 allele. Assays included cell‐survival curves, studies of potentially lethal damage repair, measurement of chromosomal aberrations and of G1 arrest, and Western blot analysis of lysates of irradiated cells to determine the phosphorylation of the product of the human Mdm2 gene (HDM2).Results: Both ATM and BRCA1 mutations were associated with sensitivity to ionizing radiation, deficient repair of potentially lethal damage and markedly increased chromosomal aberrations. A BRCA1‐mutated tumour cell line HCC1937, like ATM mutant cells, did not exhibit a normal G1 arrest but, unlike ATM mutant cells, did exhibit phosphorylation of HDM2. Expression of wild‐type BRCA1 in HCC1937 cells partially restored radioresistance, restored repair of potentially lethal damage and markedly reduced radiation‐induced chromosomal aberrations. G1 arrest, however, was not restored by expression of BRCA1.Conclusions: The results are consistent with a model in which ATM phosphorylation of BRCA1 regulates DNA repair functions, particularly those involved in potentially lethal damage repair and chromosomal integrity, but not other aspects of the cellular response to radiation such as G1 cell cycle arrest. To the authors' knowledge, this is the first demonstration of the ability of exogenously expressed BRCA1 to restore the ability to perform potentially lethal damage repair and maintain chromosomal integrity in irradiated cells. 相似文献
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