肿瘤细胞在生长、浸润和转移过程中经历的缺氧、低糖等多种环境压力会对肿瘤细胞造成内质网应激,为应对内质网应激,肿瘤细胞会诱发未折叠蛋白反应(Unfolded protein response,UPR)。PERK通路作为激活UPR的一条关键通路可通过提高肿瘤对...肿瘤细胞在生长、浸润和转移过程中经历的缺氧、低糖等多种环境压力会对肿瘤细胞造成内质网应激,为应对内质网应激,肿瘤细胞会诱发未折叠蛋白反应(Unfolded protein response,UPR)。PERK通路作为激活UPR的一条关键通路可通过提高肿瘤对不良微环境的耐受程度、诱导新生血管生成、诱导自噬体形成、激活凋亡信号分子等促进肿瘤细胞生长、增殖、侵袭及保护性自噬,并且在UPR达到一定程度时诱导肿瘤细胞凋亡及自噬性死亡。展开更多
目的探讨香砂六君子汤对脾虚高脂血症大鼠内质网应激蛋白激酶R样内质网激酶(protein kinase R-like ER kinase,PERK)信号通路的影响。方法SD大鼠随机分为4组,即正常对照组、脾虚高脂组、香砂六君子汤组和辛伐他汀组,后3组采用饮食不节...目的探讨香砂六君子汤对脾虚高脂血症大鼠内质网应激蛋白激酶R样内质网激酶(protein kinase R-like ER kinase,PERK)信号通路的影响。方法SD大鼠随机分为4组,即正常对照组、脾虚高脂组、香砂六君子汤组和辛伐他汀组,后3组采用饮食不节加力竭游泳的复合方法造模15 d后,正常组喂饲基础饲料,其余3组喂饲高脂饲料。12周后,分别给予相对剂量药物和生理盐水。4周后,检测各组大鼠血脂含量、D-木糖排泄率,油红O染色观察肝脏脂质沉积情况,实时荧光定量PCR及Western blot法检测大鼠肝脏葡萄糖调节蛋白78(glucose regulated protein 78 kD,GRP78)、PERK和活化转录因子4(the activating transcription factor 6,ATF4)基因及蛋白表达。结果与正常对照组比较,脾虚高脂组大鼠血清脂质异常,表现为总胆固醇(cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇酯(low density lipoprotein-cholesterol,LDL-C)明显升高,高密度脂蛋白胆固醇酯(high density lipoprotein-cholesterol,HDL-C)明显降低,尿D-木糖排泄率明显降低;肝脏脂质沉积显著,可见明显脂滴;肝脏GRP78、PERK和ATF4 mRNA水平及蛋白表达水平显著升高。与脾虚高脂组比较,香砂六君子汤组和辛伐他汀组大鼠血清TC、TG、LDL-C明显降低,HDL-C明显升高,尿D-木糖排泄率明显升高;其肝脏脂质沉积情况有明显改善,脂滴不同程度减轻;肝脏GRP78、PERK和ATF4 mRNA水平及蛋白表达水平明显降低。结论香砂六君子汤可能通过调控内网应激PERK信号通路来纠正脾虚脂质紊乱的状态。展开更多
Summary: Abnormal cholesterol metabolism is associated with an elevated risk of developing athero- sclerosis, hypertension, and diabetes etc. Na+/K+-ATPase was found to regulate cholesterol synthesis, distribution ...Summary: Abnormal cholesterol metabolism is associated with an elevated risk of developing athero- sclerosis, hypertension, and diabetes etc. Na+/K+-ATPase was found to regulate cholesterol synthesis, distribution and trafficking. This study aimed to examine the effect of high-fat diet on cholesterol me- tabolism in rats and the role of Na+/K+-ATPase/Src/ERK signaling pathway in the process. Forty male SD rats were evenly divided into high-fat diet group and control group at random. Animals in the former group were fed on high-fat diet for 12 weeks, and those fed on basic diet served as control. Blood lipids, including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesteral (LDL-C) levels, were detected at 3, 6 and 12 weeks. The ratio of cholesterol content in cytoplasm to that in cell membrane was detected in liver tissues. RT-PCR and Western blotting were used to measure the expression of lipid metabolism-associated genes (HMG-CoA reductase and SREBP-2) after 12-week high-fat diet. Na+/K+-ATPase/Src/ERK signaling path- way-related components (Na+/K+-ATPase ctl, Src-PY418 and pERK1/2) were also measured by West- ern blotting. The results showed that the serum TC, TG, and LDL-C levels were significantly higher in high-fat diet group than those in control group, while the HDL-C level was significantly lower in high-fat diet group at 6 weeks (P〈0.01). High-fat diet led to an increase in the cholesterol content in the cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to that in cell membrane was elevated over time. The expression of HMG-CoA reductase and SREBP-2 was significantly sup- pressed at mRNA and protein levels after 12-week high-fat diet (P〈0.05). Moreover, high-fat diet pro- moted the expression of Na+/K+-ATPase α1 but suppressed the phosphorylation of Src-PY418 and ERK1/2 at 12 weeks (P〈0.05). It was concluded that high-fat diet regulates choles展开更多
文摘肿瘤细胞在生长、浸润和转移过程中经历的缺氧、低糖等多种环境压力会对肿瘤细胞造成内质网应激,为应对内质网应激,肿瘤细胞会诱发未折叠蛋白反应(Unfolded protein response,UPR)。PERK通路作为激活UPR的一条关键通路可通过提高肿瘤对不良微环境的耐受程度、诱导新生血管生成、诱导自噬体形成、激活凋亡信号分子等促进肿瘤细胞生长、增殖、侵袭及保护性自噬,并且在UPR达到一定程度时诱导肿瘤细胞凋亡及自噬性死亡。
基金supported by a grant from the National Natural Science Foundation of China(No.81200637)
文摘Summary: Abnormal cholesterol metabolism is associated with an elevated risk of developing athero- sclerosis, hypertension, and diabetes etc. Na+/K+-ATPase was found to regulate cholesterol synthesis, distribution and trafficking. This study aimed to examine the effect of high-fat diet on cholesterol me- tabolism in rats and the role of Na+/K+-ATPase/Src/ERK signaling pathway in the process. Forty male SD rats were evenly divided into high-fat diet group and control group at random. Animals in the former group were fed on high-fat diet for 12 weeks, and those fed on basic diet served as control. Blood lipids, including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesteral (LDL-C) levels, were detected at 3, 6 and 12 weeks. The ratio of cholesterol content in cytoplasm to that in cell membrane was detected in liver tissues. RT-PCR and Western blotting were used to measure the expression of lipid metabolism-associated genes (HMG-CoA reductase and SREBP-2) after 12-week high-fat diet. Na+/K+-ATPase/Src/ERK signaling path- way-related components (Na+/K+-ATPase ctl, Src-PY418 and pERK1/2) were also measured by West- ern blotting. The results showed that the serum TC, TG, and LDL-C levels were significantly higher in high-fat diet group than those in control group, while the HDL-C level was significantly lower in high-fat diet group at 6 weeks (P〈0.01). High-fat diet led to an increase in the cholesterol content in the cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to that in cell membrane was elevated over time. The expression of HMG-CoA reductase and SREBP-2 was significantly sup- pressed at mRNA and protein levels after 12-week high-fat diet (P〈0.05). Moreover, high-fat diet pro- moted the expression of Na+/K+-ATPase α1 but suppressed the phosphorylation of Src-PY418 and ERK1/2 at 12 weeks (P〈0.05). It was concluded that high-fat diet regulates choles