内质网应激反应在严重烧伤大鼠心肌细胞凋亡中的作用

目的内质网应激反应(endoplasmic reticulum stress,ERS)介导的凋亡是真核细胞重要凋亡途径之一,通过观察严重烧伤大鼠心肌ERS不同通路蛋白表达变化,探讨其在心肌细胞凋亡中的可能作用。方法雄性7周龄Wistar大鼠64只,体重200～220 g;随机分为两组,每组32只。实验组大鼠背部制备30%体表面积Ⅲ度烫伤;对照组制备假伤模型。伤后1、4、7、14 d两组各处死8只大鼠取心肌组织,透射电镜观察心肌超微结构变化,TUNEL法检测心肌细胞凋亡,Western blot检测ERS相关蛋白,如葡萄糖调节蛋白78(glucose regulated protein 78,GRP 78)、C/EBP同源蛋白(C/EBP-homologous protein,CHOP)、半胱氨酸天冬氨酸蛋白酶12(Caspase 12)剪切体表达变化。结果大鼠均存活至实验结束。透射电镜观察示实验组大鼠心肌细胞呈凋亡改变。伤后各时间点实验组心肌细胞凋亡指数均明显高于对照组(P<0.05),伤后1、4、7 d凋亡指数逐渐升高,14 d时下降,各时间点间比较差异均有统计学意义(P<0.05)。实验组心肌细胞GRP78、CHOP及Caspase 12剪切体蛋白表达持续升高,其中各时间点GRP 78及Caspase 12剪切体表达均较对照组显著升高,差异有统计学意义(P<0.05);除伤后1 d外,其余各时间点实验组CHOP蛋白表达均较对照组升高(P<0.05)。结论严重烧伤后大鼠心肌发生ERS,其中CHOP、Caspase 12介导的凋亡通路活化,ERS可能是心肌细胞凋亡的途径之一。     

磨损微粒引起的成骨细胞内质网应激反应在骨溶解中的作用及机制研究

目的：分析内质网应激反应在骨溶解骨组织中成骨细胞凋亡和骨溶解发生发展中的作用,探讨人工关节松动的原因,为人工关节松动的防治提供新的思路和理论依据。方法：采用小鼠颅骨建立磨损微粒诱导骨溶解的动物模型,随机分成4组,每组7只：组1,空白对照组;组2,磨损微粒TiAl6V4纳米合金粉末（TiNPs）组;组3,内质网应激反应阳性对照（TiNPs+Tg）组;组4,内质网应激反应抑制剂（TiNPs+4-PBA）组。通过甲苯胺蓝染色、HE染色和ALP染色观察骨溶解的病理变化;Western Blotting方法检测骨溶解颅骨组织中内质网应激反应标志蛋白的表达变化;TUNEL和Caspase-3免疫组化方法检测骨溶解颅骨组织内成骨细胞的凋亡情况。结果：磨损微粒TiNPs能够在体外诱导骨溶解的发生、加重炎症细胞的浸润以及抑制成骨细胞分化成熟,同时磨损微粒还可以上调成骨细胞内质网应激反应标志蛋白以及促进骨溶解骨组织中成骨细胞的凋亡。在磨损微粒TiNPs的基础上加入内质网应激的抑制剂（4-PBA）后,骨溶解症状明显缓解,骨侵蚀和炎症浸润显著降低,成骨细胞的分化成熟得到改善,凋亡的成骨细胞急剧减少,内质网应激标志蛋白的表达也逐渐减弱。结论：内质网应激参与骨溶解的形成并在骨溶解的发生发展中发挥重要作用。同时,内质网应激可作为一种新的治疗靶点,为临床逆转或治疗骨溶解和无菌性松动提供新的思路和方法。     

内质网应激在高糖培养加重神经细胞缺氧-复氧损伤中的作用

目的研究内质网应激在高糖培养加重神经细胞缺氧-复氧损伤中的作用。方法在含10%胎牛血清的DMEM/F12培养基中培养小鼠神经瘤母细胞N2a,按照接种密度每毫升105个将细胞接种于培养板中。采用随机数字分组法将细胞分为四组:正常糖对照组(NC组)、正常糖缺氧-复氧组(NH组)、高糖对照组(HC组)、高糖缺氧-复氧组(HH组)。待细胞贴壁后,将DMEM/F12培养基更换为高糖培养基,孵育48h,造高糖孵育模型。在缺氧小室中缺氧3h后,再转入正常氧孵育箱中复氧2h,造缺氧-复氧损伤模型。NC组未作处理;NH组行缺氧-复氧处理;HC组行高糖孵育处理;HH组先行高糖孵育48h后,再作缺氧-复氧处理。采用CCK-8法检测细胞活力,流式细胞仪检测细胞凋亡率,Western blot法检测细胞GRP78、CHOP蛋白含量。结果与NC组和HC组比较,NH组和HH组细胞活力明显减弱,凋亡率明显升高,GRP78、CHOP蛋白含量明显增多(P0.01);与NH组比较,HH组细胞活力明显减弱,凋亡率明显升高,GRP78、CHOP蛋白含量明显增多(P0.05)。结论高糖培养加重神经细胞缺氧-复氧损伤,可能与内质网应激标志性蛋白GRP78蛋白含量增多和促凋亡转录因子CHOP介导的细胞凋亡相关。     

内质网应激与脑缺血/再灌注损伤

背景 近几年脑缺血/再灌注损伤(ischemia/reperfusion injury,URI)造成神经元凋亡的机制被广泛研究.钙离子平衡发生紊乱、活性氧生成增多等因素,都可能造成内质网内大量的未折叠蛋白质或错误折叠蛋白质的堆积,导致内质网应激(endoplasmic reticulum stress,ERS)的发生.许多研究表明脑I/RI可以诱发ERS,进而导致神经元的凋亡. 目的 对近年来ERS与脑I/RI之间的联系进行综述,希望为临床治疗提供一些新的方案,也为新药的开发提供新的思路. 内容 综述ERS诱导细胞凋亡的不同途径之间的关联及其与脑FRI的内在联系. 趋向 仍需对ERS和脑I/RI之间的联系做进一步探究,以希望通过减弱ERS来改善患者的预后.     

衣霉素诱导内质网应激对树突状细胞成熟分化的影响

目的:内质网应激(ERS)是真核细胞中普遍存在的适应性应激反应,本研究应用ERS特异性诱导剂衣霉素(TM)体外刺激小鼠脾脏树突状细胞(DC),观察DC功能状态的改变情况.方法:分离正常BALB/c小鼠脾脏DC进行体外培养,给予ERS特异性诱导剂TM刺激,观察不同剂量、不同作用时间TM刺激与DC表面共刺激分子表达及分泌功...     

番茄红素对缺氧/复氧诱导小鼠心肌细胞内质网应激和凋亡的影响

目的 评价番茄红素对缺氧/复氧(hypoxia/reoxygenation,H/R)引起的小鼠心肌细胞内质网应激(endoplasmic reticulum stress,ERS)和凋亡的影响. 方法 建立C57BU6乳鼠心肌细胞H/R模型,采用随机数字表法将C57BL/6小鼠心肌细胞分为正常对照组(C组)、番茄红素组(Lyc组,含5μmol/L番茄红素的培养基预处理4h)、H/R组(H/R组,缺氧4h复氧6h)和番茄红素+H/R组(Lyc+H/R组,给予5μmol/L番茄红素预处理4h后行H/R处理).采用水溶性四氮唑-8(cell counting Kit-8,CCK-8)法检测心肌细胞存活率,倒置显微镜下观察细胞搏动频率,TUNEL法检测细胞凋亡率,二氯荧光素法(dichlomnuorescein diacetate,DCFH-DA)检测细胞内活性氧(reactive oxygen species,ROS)含量,实时荧光定量PCR (real-time PCR)检测葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)及半胱天冬氨酸蛋白酶-12 (cysteme aspartate specific protease-12,caspase-12)mRNA的表达,Western blot法分析剪切的半胱天冬氨酸蛋白酶-12(cleaved cysteme aspartate specific protease-12,Cleaved-caspase-12)和剪切的半胱天冬氨酸蛋白酶-3(cleaved cysteme aspartate specific protease-3,Cleaved-caspase-3)的表达. 结果 与C组比较,H/R组心肌细胞存活率显著降低[(100±5)％,(69±6)％](P＜0.01),搏动频率显著降低[(94±6),(28±5)次/min](P＜0.01),心肌细胞凋亡率[(4.9±1.5)％,(25.6±2.6)％]和ROS含量[(100±11)％,(226±10)％]显著升高(P＜0.01);CHOP mRNA[(1.00±0.10)、(2.60±0.19)]和GRP78 mRNA[(1.00±).18)、(4.12±0.23)]表达水平显著升高(P＜0.05);caspase-12 mRNA[(1.00±0.09)、(1.79±0.14)]、Cleaved-caspase-12[(1.00±0.08)、(1.85±0.10)]和Cleaved-caspase-3[(1.00±0.07)、(1.89±0.14)]表达水平显著升高(P＜0.05).与H/R组比较,Lyc+H/R组心肌细胞存活率明显升高[(69±6)％、(84±7)％](P＜0.05),搏动频率增加[(28±5)、(73±6)次/min] (P＜0.05),凋亡率显著降低[(25.6±2.6)％,(18.2±2.2)％](P＜0.05),细胞内ROS含量[(226±10)％、(140±16)％]明显降低,CHOP mRNA [(2.60±0.19)、(1.71±0.14)]和GRP78 mRNA[(4.12±0.23),(1.98±0.19)]表达水平显著降低(P＜O.05);caspase-12 mRNA[(1.79±0.14)、(1.38±0.11)]、Cleaved-caspase-12[(1.85±0.10)、(1.26±0.12)]和Cleaved-caspase-3[(1.89±0.14)、(1.36±0.12)]表达水平显著降低(P＜0.05). 结论 番茄红素可抑制H/R过程中的ERS及其凋亡信号途径而减轻心肌细胞损伤.     

Ubiquitination and endoplasmic reticulum stress of renal intrinsic cells in hyperglycemia

Objective To investigate the effects of hyperglycemia on ubiquitination and endoplasmic reticulum stress in renal intrinsic cells (podocytes and proximal tubular epithelial cells) and its role in pathogenesis of diabetic nephropathy. Methods Diabetic mice were induced by streptozotocin injection. After 16 weeks of hyperglycemia, immunofluorescence was used to detect the expressions of ubiquitination and glucose-regulating protein 94 (GRP94) in renal cortex and medulla area of kidney sections. Primary mouse podocyte and proximal tubular epithelial cells were isolated by flow cytometry, and exposed to 30 mmol/L glucose for indicated time (1 d, 3 d and 7 d). Their ubiquitination and GRP94 expressions were evaluated by Western blotting. Results Diabetic mice presented microalbuminuria and slightly widened mesangium was found in glomerular area. Ubiquitinated proteins, mainly localized in podocytes and tubular epithelial cells, exhibited an apparently higher expression in diabetic mice than control mice (all P＜0.05). Hyperglycemia promoted the ubiquitination in a time-dependent manner. Compared with their normal cells, primary mouse podocyte and primary tubular epithilial cells treated with high glucose for 3 d and 7 d showed increased ubiquitinated protein (all P＜0.05). GRP94 was interspersed in podocytes and proximal tubular epithelial cells. Expression of GRP94 was significantly increased in glomerular area of diabetic mice and podocyte with 3 and 7 day-high glucose as compared with those in their control groups (all P＜0.05). GRP94 expression had no significant change in tubular area and tubular epithilial cells treated with high glucose. Conclusions Hyperglycemia may lead to accumulation of ubiquitinated proteins in intrinsic kidney cells. The imbalance of protein homeostasis in podocyte may contribute to podocyte injury during the onset of diabetic nephropathy.     

Effect of endoplasmic reticulum stress on the activation of high glucose-induced monocytes

Objective To observe the effects of endoplasmic reticulum stress (ERS) on the activation of monocytes induced by high glucose and explore the underlying mechanism. Methods The monocyte cell line THP-1 was stimulated with high glucose, and then treated with molecular chaperone betaine. The levels of glucose regulation protein 78 (GRP78) and p-JNK, which were associated with ERS were detected by real-time PCR and Western blotting. The proliferation of the cell line was detected by MTT method. Transwell and immunofluorescence were applied to observe the chemotaxis and phenotype of cells respectively. Results The levels of GRP78 and p-JNK of THP-1 cells stimulated by high glucose were significantly increased compared with the normal control group (all P＜0.05). The proliferation and chemotactic were also enhanced (all P＜0.05). The number of cells in M1 phenotype was increased remarkably (P＜0.05). All the indexes above could be rescued by betaine. Conclusion The activation of THP-1 cells can be induced by high glucose through ERS, while molecular chaperone betaine can reverse the activation.     

Hepatic autophagy after severe burn in response to endoplasmic reticulum stress

Background

Previous studies showed that liver dysfunction develops soon after severe burn, and this is associated with activation of endoplasmic reticulum (ER) stress. Autophagy is a catabolic process to maintain cellular organelle balance; ER stress is associated with autophagy signaling cascades. We thus sought to determine whether autophagy signals were associated with damage in the liver after burn, and further whether burn-associated ER stress activates autophagy signals in hepatocytes.

Methods

C57BL/6 male mice received a 25% total body surface area full-thickness scald burn, and liver was harvested at 24 h after burn. HepG2 cells were stimulated with an ER stress inducer thapsigargin (TG) for 24 h to mimic ER stress in vitro. Terminal deoxyuridine nick-end labeling staining was performed on histologic sections of liver. Autophagy was assessed by immunoblotting. Statistical analysis was performed using the Student t-test and significance was accepted at P < 0.05.

Results

Terminal deoxyuridine nick-end labeling positive–stained hepatocytes increased in burned animals with a significant elevation of caspase 3 activity (P < 0.05). Hepatic autophagy-related (ATG) protein 3, ATG5 and light chain (LC) 3B elevated significantly in burn animals as well (P < 0.05). Expression of Beclin-1, LC3A, and LC3B increased in HepG2 cells in response to TG, similar to the response seen in vivo. Cytosolic adenosine triphosphate dropped significantly, and adenosine monophosphate–activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were phosphorylated as well in response to TG (P < 0.05).

Conclusions

ER stress, which occurs in hepatocytes after severe injury, is associated with autophagy and liver damage after severe burn. In response to ER stress, activated autophagy is associated with adenosine monophosphate–activated protein kinase and mammalian target target of rapamycin pathway.     

内质网应激与缺血后处理的心肌保护

内质网应激(endoplasmic reticulum stress,ERS)是细胞对各种伤害性刺激的适应性反应.在心肌缺血/再灌注(ischemia/reperfusion,I/R)过程中,过度的ERS引起心肌细胞凋亡导致心肌损伤.缺血后处理(ischemic postconditioning,I-postC)是心肌对抗I/R损伤的内源性保护现象,可通过多条信号转导途径发挥心肌保护作用,对ERS的调节是其重要方面.现将从ERS的角度探讨I-postC的心肌保护机制.     

Cyclic stretch-induced apoptosis in rat annulus fibrosus cells is mediated in part by endoplasmic reticulum stress through nitric oxide production

Various mechanical stresses in vivo induce disc cell apoptosis and intervertebral disc (IVD) degeneration, but the underlying molecular mechanism is not fully known. The aim of this study was to investigate the role of endoplasmic reticulum stress in cyclic stretch-induced apoptosis of rat annulus fibrosus (AF) cells. Flexercell Tension Plus system was used to apply cyclic stretch to rat annulus fibrosus cells at a frequency of 0.5 Hz with 20% elongation for 12, 24, 36, or 48 h. Apoptosis was detected by flow cytometry, and nuclei morphologic changes were visualized by Hoechst 33258 staining and caspase-8, 9 activity assays. The expression of the markers of endoplasmic reticulum stress including CHOP, GRP78, and caspase-12 were determined by RT-PCR and Western blot. Mitochondrial membrane potential change was observed by JC-1 staining in situ. In addition, the levels of the nitric oxide (NO) were determined with the Griess reaction and fluorescence staining. The results indicated that cyclic stretch at a frequency of 0.5 Hz with 20% elongation-induced apoptosis in rat AF cells. Prolonged exposure of the unphysiologically cyclic stretch to AF cells caused NO overproduction, up-regulation of endoplasmic reticulum stress markers including CHOP, GRP78, and caspase-12, depolarization of mitochondria and activation of caspase-9. However, cyclic stretch at this level had no effect on caspase-8 activity. In addition, specific inhibitor of caspase-12 (Z-ATAD-FMK) and caspase-9 (Z-LEHD-FMK) partly suppressed cyclic stretch-induced AF cell apoptosis and the anti-apoptotic effects of the caspase inhibitors were additive. Our data suggest that endoplasmic reticulum stress, likely mediated by NO, contributes to the AF cell apoptosis induced by cyclic stretch in addition to the mitochondrial pathway. These findings could be helpful to understand the mechanism of disc cell apoptosis, the root cause of IVD degeneration.     

氢气对PC12细胞缺氧复氧时内质网应激的影响

目的 探讨氧气对PC1 2细胞缺氧复氧时内质网应激的影响.方法 PC12细胞采用随机数字表法,将其随机分为4组,正常对照组:细胞常规培养25 h;阳性对照组:细胞正常培养1h后,用氧气饱和的RPM1-1640培养基继续培养24 h;缺氧复氧组:细胞缺氧1h后复氧24 h;氢气组:细胞缺氧1 h后,州氧气饱和的RPM1,1640培氧基复氧24 h.PC12细胞加入含Na2S2O4终浓度为5.0mmol/L的RPMI-1640培养液,5％ CO2培养箱37 ℃孵育1h;更换正常RPMI-1640培养液,继续培养24h,制备PC12细胞缺氧复氧模型.采用WST-1法测定细胞相对增殖率,采用硫代巴比妥酸法测定MDA浓度,采用免疫组化法检测caspase-3表达,采用RT-PCR法检测活化转录因子4(ATF4)mRNA和C/EBP同源蛋白(CHOP)mRNA的表达.结果 与正常对照组和阳性对照组比较,缺氧复氧组细胞相对增殖率降低,MDA浓度升高,caspase-3、ATF4 mRNA和CHOP mRNA的表达七调,氧气组ATF4 mRNA和CHOP mRNA的表达上调(P＜0.05);正常对照组和阳性对照组间细胞相对增殖率、MDA浓度、caspase-3 、ATF4nRNA和CHOP mRNA的表达比较差异无统计学意义(P＞0.05);与缺氧复氧组比较,氢气组细胞相对增殖率升高,MDA浓度降低,caspase-3、ATF4 mRNA和CHOP mRNA的表达下调(P＜0.05).结论 氧气可能通过抑制内质网应激,降低细胞凋亡,减轻PC12细胞缺氧复氧损伤.     

内质网应激介导吡格列酮在趋化素诱导成骨细胞代谢过程中的作用机制

目的 观察吡格列酮（Pioglitazone）对趋化素诱导成骨细胞代谢过程中的影响,探讨吡格列酮改善成骨细胞凋亡的信号转导机制。方法 将成骨细胞随机分组,选取适宜浓度的趋化素（Chemerin）进行诱导后,加入吡格列酮,观察成骨细胞活力变化。ELISA 法检测细胞趋化蛋白1（MCP-1）、E选择素（E-selection）的的影响,采用Western blot法检测成骨细胞黏附分子1（ICAM-1）、需肌醇跨膜激酶/核酸内切酶1(inositol-requiring transmembrane kinase/endonuclease 1,IRE1)、葡萄糖调节蛋白78（Glucose-regulated protein 78,GRP78）的表达变化,探究内质网应激反应在此过程中作用。结果 MTT法检测提示加入Pioglitazone后对成骨细胞活力未见明显影响;与对照组相比,成骨细胞ICAM-1、MCP-1、E-selection、IRE1、GRP78、在Chemerin组的指标较高(P<0.05）,而 Pioglitazone呈浓度依赖性地抑制Chemerin所诱导的上述效应,差异具有统计学意义(P<0.05),当吡格列酮浓度为20μmol/L时效果最显著。结论 内质网应激可能参与趋化素诱导成骨细胞代谢中的细胞凋亡过程,吡格列酮可抑制趋化素的作用,对成骨细胞具有保护功能,其机制可能与抑制内质网应激反应相关。     

内质网应激在白蛋白诱导肾小管上皮细胞凋亡中的作用

目的 探讨内质网应激在白蛋白超负荷诱导肾小管上皮细胞凋亡中的作用和分子机制。 方法 Western印迹法检测肾小管上皮细胞（HKC）内质网伴侣蛋白糖调节蛋白78（GRP78）和内质网应激蛋白CHOP（CCAAT增强子结合蛋白同源蛋白,也称为GADD153）表达与人血清白蛋白（HSA）作用时间和浓度的关系。实时荧光定量PCR法检测CHOP siRNA对CHOP基因转录的抑制情况。Western印迹法检测CHOP siRNA转染后CHOP蛋白水平的变化。膜联蛋白V和碘化丙锭（Annexin V-FITC和PI）双染的流式细胞术检测白蛋白诱导HKC凋亡的变化以及CHOP siRNA对HKC凋亡的影响。 结果 （1）分别以0、5、10、20 g/L白蛋白作用于HKC 24 h,GRP78、CHOP蛋白表达及细胞凋亡均随白蛋白浓度的增加而上调,各组间差异有统计学意义（P ＜ 0.01）;以20 g/L白蛋白分别作用于HKC 0、6、12、24、36 h,GRP78蛋白表达在6 h即显著增加,CHOP蛋白表达及HKC凋亡则在12 h显著增加,各组间差异有统计学意义（P ＜ 0.01）。（2）CHOP siRNA显著抑制白蛋白诱导的CHOP 基因转录及蛋白表达（P ＜ 0.01）,对白蛋白诱导的HKC凋亡有显著抑制作用（P ＜ 0.01）。 结论 白蛋白超负荷可诱导肾小管上皮细胞发生内质网应激,并通过上调促凋亡因子CHOP表达引起肾小管上皮细胞内质网相关的细胞凋亡,这可能是蛋白尿引起肾小管间质病变的重要机制。     

Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2

A variety of toxic insults can result in endoplasmic reticulum (ER)-stress that ultimately leads to apoptosis. -cells have a highly developed ER due to a great commitment to insulin production. The present study was carried out to determine the role of ER-stress in isolated human pancreatic islet apoptosis, and the potential protective effects of Bcl-2. Isolated human islets were infected with an adenoviral vector encoding Bcl-2 and then exposed to brefeldin-A, tunicamycin, A23187 and pro-inflammatory cytokines. Activation of caspase-12 was analyzed by means of Western blots. Apoptosis was evaluated using a commercial quantitative assay. ER-stress-inducers promoted caspase-12 activation and apoptosis, effect reversed by overexpression of Bcl-2. Co-localization of caspase-12 and Bcl-2 in the microsomal islet fractions were demonstrated by means of Western blots. We can conclude that the current studies highlight the importance of Bcl-2 as an anti-apoptotic protein, and shed new light on the mechanisms underlying its cytoprotective effects on pancreatic islets.     

Atorvastatin reduces alcohol-induced endoplasmic reticulum stress in AC16 cardiomyocytes

Objectives. To investigate the effects of atorvastatin on the ultrastructure and lipid metabolism of AC16 cardiomyocytes in response to alcohol-induced endoplasmic reticulum stress (ERS). Design. The expression of the ERS-related factor GRP78 in the established ERS model was determined by western blotting. Alcohol-exposed cardiomyocytes were treated with various concentrations of atorvastatin, and GRP78 expression was measured. Cardiomyocyte ultrastructure was observed and SREBP-1c and triglyceride (TG) levels were evaluated. Results. Exposure to ethanol for 0, 12, 24, and 48?h significantly affected GRP78 expression (0.19?±?0.02, 0.27?±?0.03, 0.39?±?0.01, and 0.64?±?0.02, respectively). GRP78 expression in the 1, 10, and 100?μmol?L^?1 atorvastatin-treated groups was 0.50?±?0.04, 0.38?±?0.03, and 0.24?±?0.01, respectively, and significantly different from control group expression (0.19?±?0.02); the expression in the alcohol group was 0.64?±?0.02. Alcohol-treated AC16 cells had significantly larger and fewer mitochondria and disorganized cristae, often replaced by vacuoles. These aberrations decreased with increasing atorvastatin concentrations. SREBP-1c expression also differed significantly among all atorvastatin-treated and control groups (0.47?±?0.04, 0.39?±?0.03, and 0.31?±?0.02; normal 0.25?±?0.02; alcohol 0.56?±?0.03). TG expression differed significantly between the 10 and 100?μmol?L^?1 groups (26.84?±?1.63, 23.11?±?2.05) and the alcohol group (36.35?±?2.41). Conclusions. Atorvastatin inhibited the expression of the ERS-related factor GRP78 in response to alcohol exposure, improved cell morphology, and enhanced lipid metabolism in a cellular model of alcoholic cardiomyopathy.     

缺血预处理调节内质网应激及促进自噬机制的研究进展

缺血预处理(IPC)对于缺血再灌注损伤(IRI)发生后更迅速的恢复生理功能和组织结构和减少损伤具有重要的作用。细胞受到外界刺激后,内质网应激(ERS)启动,可以通过减少未折叠蛋白的累积并增加未折叠蛋白的降解,保护内质网稳态,泛素化降解系统也参与其中,但当细胞受到外界刺激持续或者过强时,ERS和泛素化降解系统无法消除未折...