目的探讨PYHIN1(pyrin and HIN domain-containing protein 1)/Caspase 1炎症复合体信号通路在主动脉内皮细胞(HAEC)中的表达水平及作用机制。方法体外培养人主动脉内皮细胞,分为对照组和实验组,对照组用天然低密度脂蛋白(nLDL)处理,实...目的探讨PYHIN1(pyrin and HIN domain-containing protein 1)/Caspase 1炎症复合体信号通路在主动脉内皮细胞(HAEC)中的表达水平及作用机制。方法体外培养人主动脉内皮细胞,分为对照组和实验组,对照组用天然低密度脂蛋白(nLDL)处理,实验组用不同浓度的氧化低密度脂蛋白(oxLDL)处理诱导内皮细胞损伤,模拟动脉粥样硬化细胞模型。观察PYHIN1/Caspase 1炎症复合体的表达以及线粒体活性氧(mtROS)在内皮细胞黏附中的作用。结果与对照组相比,实验组以浓度依赖的方式促进PYHIN1、Caspase 1、IL-18和ICAM1的表达(P<0.05)。同时,实验组细胞黏附增强,mtROS显著增加,SOD活性降低;加入mtROS的抑制剂后,细胞的黏附能力降低(P<0.05)。结论oxLDL通过促进mtROS产生增强内皮细胞的黏附作用。展开更多
Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious...Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.展开更多
INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of t...INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of the gut ,it is defined as an unequivocal non-invasive epithelial change[2,3].The observation of gastric dysplasia as a cancerous lesion was recognized over a century ago ,but it is only after the advent of gastroscopy that its clinical significance has been stressed[4-7].展开更多
Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body...Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body, endosome, membrane, and mitochondria, providing lipids and proteins for the repair of these organelles. ER stress can be induced by various abnormal materials in the cell. ER stress is a compensatory intracellular environment disorder that occurs during areaction. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system, but excessive ER activation can cause cell death. The Pubmed and Web of Science databases were searched for full-text articles, and the terms "endoplasmic reticulum stress/unfolded protein response/gynecologic tumor cell apoptosis" were used as key words. Thirty-five studies of ER stress and unfolded protein response published from 2000 to 2016 were analyzed. Stress triggers apoptosis through a variety of signaling pathways. Increasing evidence has shown that the ER plays an important role in tumor cell diseases. The present review discusses the molecular mechanisms underlying unfolded protein response and its ability to promote survival and proliferation in gynecologic tumor cells.展开更多
文摘目的探讨PYHIN1(pyrin and HIN domain-containing protein 1)/Caspase 1炎症复合体信号通路在主动脉内皮细胞(HAEC)中的表达水平及作用机制。方法体外培养人主动脉内皮细胞,分为对照组和实验组,对照组用天然低密度脂蛋白(nLDL)处理,实验组用不同浓度的氧化低密度脂蛋白(oxLDL)处理诱导内皮细胞损伤,模拟动脉粥样硬化细胞模型。观察PYHIN1/Caspase 1炎症复合体的表达以及线粒体活性氧(mtROS)在内皮细胞黏附中的作用。结果与对照组相比,实验组以浓度依赖的方式促进PYHIN1、Caspase 1、IL-18和ICAM1的表达(P<0.05)。同时,实验组细胞黏附增强,mtROS显著增加,SOD活性降低;加入mtROS的抑制剂后,细胞的黏附能力降低(P<0.05)。结论oxLDL通过促进mtROS产生增强内皮细胞的黏附作用。
基金supported by the National Natural Science Foundation of China,No.81671125the Natural Science Foundation of Guangdong Province,No.2021A1515011115Guangzhou Science and Technology Project,No.202102010346(all to YZC)。
文摘Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.
基金Supported by the Science Fund of Health Department,No.95A2141.and the Science Fund of Health Bureau of Shanghai.No.982019
文摘INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of the gut ,it is defined as an unequivocal non-invasive epithelial change[2,3].The observation of gastric dysplasia as a cancerous lesion was recognized over a century ago ,but it is only after the advent of gastroscopy that its clinical significance has been stressed[4-7].
文摘Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body, endosome, membrane, and mitochondria, providing lipids and proteins for the repair of these organelles. ER stress can be induced by various abnormal materials in the cell. ER stress is a compensatory intracellular environment disorder that occurs during areaction. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system, but excessive ER activation can cause cell death. The Pubmed and Web of Science databases were searched for full-text articles, and the terms "endoplasmic reticulum stress/unfolded protein response/gynecologic tumor cell apoptosis" were used as key words. Thirty-five studies of ER stress and unfolded protein response published from 2000 to 2016 were analyzed. Stress triggers apoptosis through a variety of signaling pathways. Increasing evidence has shown that the ER plays an important role in tumor cell diseases. The present review discusses the molecular mechanisms underlying unfolded protein response and its ability to promote survival and proliferation in gynecologic tumor cells.
