ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium i

来源 :中国环境诱变剂学会第七届全国会员代表大会暨第十七次学术大会 | 被引量 : 0次 | 上传用户:bocha007
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
  Cadmium(Cd)is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs.The previous studies showed that Cd could induce DNA damage and autopahgy.Autophagy can stabilize genetic material and DNA integrity.The aim of present study was going to explore the exact mechanism and role of autophagy induced by Cd in spermatozoa cells.Mouse spermatocyte derived cells(GC-2)were treated by Cd chloride 20 μM for 24 h.The level of ROS,DNA damage,autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase(AMPK)/mTOR were determined.The results showed that Cd induced autophagy and DNA damage in GC-2 cells via ROS generation,and the autophagy signal pathway of AMPK/mTOR was activated by ATM which is the sensor of DNA damage.Melatonin,a well known antioxidant,could ameliorate DNA damage,and inhibit autophagy via AMPK/mTOR signal pathway.Furthermore,after inhibition of autophagy by knockdown AMPKα,the increased DNA damage was observed by Cd treatment in GC-2 cells.These findings demonstrated the protective role of autophagy in DNA damage and suggested the mechanism of autophagy induced by Cd through ATM/AMPK/mTOR signal pathway in spermatozoa cells.
其他文献
Hexavalent chromium(Cr(Ⅵ))is a potent human lung carcinogen,and numerous epidemiological studies have been performed to determine its carcinogenicity.While Cr(Ⅵ)-induced DNA damage has been well-docum
Chronic exposure to heavy metal is a worldwide health concern for many diseases:hematologic diseases,neurological disorders,Immune diseases and cancer.Cancer is commonly considered to be developed fro
目的:探讨LincRNA-p21通过p21诱导食管癌细胞周期阻滞的调控及其可能的机制.方法:应用RT-qPCR技术,检测LincRNA-p21在两株食管癌细胞株(EC109和EC9706)与一株永生化食管上皮细胞(Het-1A)中的表达情况.过表达LincRNA-p21及其阴性对照的慢病毒成功转染食管癌EC109后,通过流式细胞术检测食管癌EC109细胞的周期分布,EdU染色法分析EC109细胞的
目的:研究亚砷酸钠对人正常膀胱上皮(SV-HUC-1)细胞中原癌基因表皮生长因子受体2(HER2)和热应激蛋白HSP90,生长转移抑制因子NDRG1,白介素6(IL-6)表达的影响.方法:将处于对数生长期的SV-HUC-1细胞进行急性染毒,暴露于含终浓度为0(对照)、1、2、4、8、10μmol/L亚砷酸钠的培养基染毒24h.24h后提取细胞总蛋白采用western blot方法检测细胞P-HER
目的:探究砷暴露对THP-1巨噬细胞氧化应激和ABCA1基因表达的影响以及诱导细胞凋亡的可能机制.方法:分别以0μM、4μM、8μM、12μM次砷酸钠暴露THP-1巨噬细胞48h,NADPH氧化酶(NOX)抑制剂二联苯碘(DPI)和抗氧化剂N-乙酰半胱氨酸(NAC)预处理细胞1h,CCK-8检测细胞生存率,流式细胞术DCFH-DA染色法检测细胞内活性氧的生成量,免疫荧光检测细胞内p47phox在细
目的:3,3,-二吲哚基甲烷(DIM)是十字花科植物的主要代谢产物之一,作为一种天然植物化学物的代表,具有显著的肿瘤预防作用.本研究拟探讨DIM对胃癌细胞的抑制效应与作用机制,以及其过程中自噬水平的改变.方法:为评价DIM对胃癌细胞的体外实验效应,选取BGC-823和SGC-7901作为胃癌细胞株,用0、40、60、80μM剂量的DIM处理这两种胃癌细胞48h后,分别用CCK-8试剂盒与平板克隆实
This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosen
目的:探讨孕期PM2.5气管暴露对孕鼠结肠肠道菌群和短链脂肪酸的影响及槲皮素的干预效果.方法:将健康ICR孕鼠随机分为空白对照组、PM2.5模型对照组和低、中、高三个槲皮素干预组.于孕3、6、9、12、15天分别进行气管滴注,除空白对照组外,其余各组滴注PM2.5溶液(15mg/kg),空白组给予相应剂量的干净滤膜洗脱液;各组孕鼠于孕期每天灌胃,空白对照组和PM2.5模型组给予0.15%羧甲基纤维
[目的]先前的研究表明姜黄素具有潜在的抗肿瘤活性,然而其分子机制尚不清楚,本旨在探究细胞自噬在姜黄素细胞凋亡中的作用及其潜在的分子机制.[方法]MTT法检测细胞活力,Hoechst33342及AV/PI法检测细胞凋亡,Rh123法检测线粒体膜电位,MDC法荧光检测自噬酸性小体,westernblot法检测相关蛋白表达.[结果]与对照组相比,不同浓度姜黄素(5、10、20、40及60μM)处理24h
[目的]观察不同时点900MHz微波辐射对睾丸组织活性氧水平、抗氧化酶活性和组织形态的影响。研究机体对微波辐射的敏感时间窗,为进一步了解移动通讯微波辐射的生物效应和健康影响提供实验资料。[方法]健康雄性SD大鼠110只,在光暗周期为12h:12h的光制(光照时间为9AM到9PM)下饲养30d培养昼夜节律,光照强度为250~350Lux,随后利用自发活动视频分析系统对动物进行24h自发活动观测,以平