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| 1 | 心脏细胞衰老与Uvrag基因的缺失显示文摘背景:前期工作发现自噬相关基因Uvrag缺失导致年龄相关心肌病,但细胞衰老在此过程中的作用尚不清楚。目的:研究Uvrag基因缺失对心脏细胞衰老的影响。方法:从Uvrag基因缺失纯合子小鼠和野生型小鼠中各取14只雄性小鼠分两批分别饲养到3月龄和8月龄。采用real time RT-PCR检测小鼠心脏组织衰老相关分泌表型相关因子mRNA表达变化,苏木精-伊红染色、天狼猩红染色、衰老相关β-半乳糖苷酶染色进行心肌组织学观察,透射电镜观察小鼠心肌细胞超微结构的变化,蛋白免疫印迹检测小鼠心脏组织p53蛋白表达量。实验方案经上海交通大学动物实验伦理委员会批准。结果与结论:①苏木精-伊红染色和天狼猩红染色结果显示,Uvrag基因缺失导致单个心肌细胞显著增大及心脏纤维化;②透射电镜显示,Uvrag基因缺失小鼠心肌细胞线粒体形态异常、排列紊乱,肌浆网肿胀;③衰老相关β-半乳糖苷酶染色发现,Uvrag基因缺失小鼠心脏衰老细胞显著增多;④real time RT-PCR结果表明,Uvrag基因缺失小鼠心脏衰老相关分泌表型因子表达显著上调;⑤Western blot结果显示Uvrag基因缺失导致心脏组织衰老调控关键蛋白p53表达显著升高;⑥结果说明,自噬相关基因Uvrag缺失促进小鼠心脏细胞衰老;Uvrag基因是潜在的延缓心脏衰老及抗衰老相关心脏疾病的靶分子。 | 来帅威 张沙沙 刘晓芸 Haniya Mazhar Amber Naz 贺林 朱洪新 | 2021 | 中国组织工程研究2021，25，14： | 3 |
| 2 | UVRAG基因缺失促进饥饿诱导的肝脏脂肪变性显示文摘[目的]紫外线辐射耐受相关(ultraviolet resistance-associated gene,UVRAG)是一个自噬相关基因,具有多种生物学功能.利用UVRAG基因缺失的小鼠证实了该基因缺失可阻断体内自噬流,并鉴于自噬对脂代谢有一定调控作用,研究了UVRAG在饥饿诱导的肝脏脂肪变性中的作用.[方法与结果]野生型小鼠和UVRAG基因缺失小鼠给予正常饮食或24 h饥饿处理.在正常生理条件下,油红染色显示UVARG基因缺失小鼠和野生型小鼠肝脏无明显脂质积聚;但是在24 h饥饿条件下,该基因缺失可导致肝脏脂质积聚显著增多,且UVRAG基因缺失小鼠肝脏甘油三酯、游离脂肪酸质量比显著升高,而总胆固醇质量比无显著性差异.实时荧光定量聚合酶链式反应(reverse transcription-polymerize chain reaction,RT-PCR)显示,在正常生理条件下的胆固醇调节元件结合蛋白-1(sterol regulatory element-binding protein1,SREBP-1)基因在UVRAG基因缺失小鼠肝脏表达显著下调,但在饥饿条件下,UVARG基因缺失小鼠和野生型小鼠肝脏SREBP-1表达无显著差异;而在实验组和对照组中其他肝脏脂代谢相关基因CD 36,FAS,CPT-1,PPAR和FGF 21的表达无显著性变化.此外,UVARG基因缺失对脂代谢调控分子AMPK活性无显著影响.在饥饿条件下,UVRAG基因缺失可导致血浆甘油三酯和游离脂肪酸浓度上升,血糖浓度下降.[结论]UVARAG基因缺失促进饥饿诱导的肝脏脂肪变性,这可能与肝脏自噬阻断和肝脏摄取血浆游离脂肪酸增多有关. | 胡晓雯 张沙沙 安琳 AMBER Naz 朱洪新 | 2018 | 上海大学学报(自然科学版)2018，24，3： | 2 |
| 3 | 自噬相关基因Rubicon缺失可抑制心脏细胞衰老显示文摘背景:心脏衰老是心脏疾病的主要危险因素之一,而细胞衰老是心脏衰老的主要机制,在衰老相关心脏疾病中起重要作用。作者前期工作发现自噬相关基因Uvrag缺失促进小鼠心脏细胞衰老,Rubicon是Uvrag的抑制性互作蛋白,其对小鼠心脏细胞衰老的作用尚不明确。目的:探讨Rubicon基因对心脏细胞衰老的影响。方法:使用15月龄野生型小鼠、Rubicon基因缺失小鼠、Uvrag基因缺失小鼠作为观察对象,其中Uvrag基因缺失小鼠作为阳性对照。采用荧光定量PCR检测小鼠心脏组织衰老相关分泌表型相关因子mRNA表达变化,苏木精-伊红染色、天狼猩红染色、衰老相关β-半乳糖苷酶染色进行心肌组织学观察,蛋白免疫印迹检测小鼠心脏组织p53和p16蛋白表达量。实验方案经上海交通大学动物实验伦理委员会批准。结果与结论:①苏木精-伊红染色和天狼猩红染色结果显示,Rubicon基因缺失改善了衰老过程中心肌细胞重塑及心脏纤维化;②衰老相关β-半乳糖苷酶染色发现,Rubicon基因缺失小鼠心脏衰老细胞较野生型对照组显著减少(P<0.05);③荧光定量PCR结果表明,Rubicon基因缺失小鼠心脏白细胞介素1β、白细胞介素6、转化生长因子β和Ⅲ型胶原α1链、基质金属蛋白酶组织抑制因子1 mRNA表达量较野生型对照组显著下调(P<0.05);④免疫印迹结果显示,Rubicon基因缺失导致心脏组织衰老调控关键基因p53表达较野生型对照组显著降低(P<0.05);⑤提示Rubicon基因缺失可显著抑制小鼠心脏细胞衰老并延缓心脏衰老,Rubicon是潜在的抑制心脏细胞衰老、抗心脏衰老及衰老相关心脏疾病的靶分子。 | 何帆 来帅威 张沙沙 董凡 Amber Naz Haniya Mazhar 贺林 朱洪新 | 2022 | 中国组织工程研究2022，26，24： | 1 |
| 4 | Rubicon deficiency exacerbates fasting-induced hepatic steatosis显示文摘Objective: Rubicon is an inhibitory interacting protein of the autophagy-related protein Uvrag. We previously showed thatRubicon deficiency promotes autophagic fluxin vivo and that autophagy can degrade lipid droplets. This study aimed to investigate the effects of Rubicon deficiency on fasting-induced hepatic steatosis.Methods: Two-month-old wild-type (WT) andRubicon-deficient mice were subjected to feeding or fasting for 24 hours to induce hepatic steatosis. The distribution of liver lipid droplets was revealed by oil red O staining. Hepatic and plasma triglyceride, non-esterified fatty acid (NEFA), and cholesterol levels were detected using commercially available kits. Real-time reverse transcriptasepolymerase chain reaction was performed to analyze the mRNA expression of genes related to lipid metabolism in the liver. Western blot was conducted to assess autophagy-related protein levels in the liver. The animal experiments were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University, China.Results: We showed that under fasting conditions,Rubicon-deficient mice had more lipid droplets in the liver than WT controls. Consistent with these results, the hepatic triglyceride, NEFA, and cholesterol levels in fastedRubicon-deficient mice were significantly higher than those of fasted WT controls. The levels ofSREBP-1, a key regulator of lipid synthesis, were significantly lower in livers from fasted WT mice than those of fed WT mice. However, the decrease inSREBP-1 in fasted mice was attenuated byRubicon deficiency. Western blot analysis demonstrated that the fasting-induced increase in autophagic flux was amplified byRubicon deficiency. Finally, we showed thatRubicon deficiency in mice led to elevated plasma triglyceride and NEFA acid levels under fasting conditions.Conclusion: Rubicon deficiency exacerbates fasting-induced hepatic steatosis in mice. | Fan Dong Xiao-Wen Hu Shasha Zhang Fan He Amber Naz Lin He Hongxin Zhu | 2022 | Journal of Bio-X Research2022，5，1： | 0 |
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