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Resveratrol reduces brain injury after subarachnoid hemorrhage by inhibiting oxidative stress and endoplasmic reticulum stress

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Neural Regeneration Research 2019年第10期14卷 1734-1742页

作者： Yun-Kai Xie Xin Zhou Hong-Tao Yuan Jie Qiu Dan-Qing Xin Xi-Li Chu Da-Chuan Wang Zhen Wang Department of Physiology School of Basic Medical SciencesShandong UniversityJinanShandong ProvinceChina Department of Spinal Surgery Shandong Provincial Hospital Affiliated to Shandong UniversityJinanShandong ProvinceChina

Previous studies have shown that resveratrol,a bioactive substance found in many plants,can reduce early brain injury after subarachnoid hemorrhage,but how it acts is still *** study explored the mechanism using the experimental subarachnoid hemorrhage rat model established by injecting autologous blood into the cerebellomedullary *** models were treated with an intraperitoneal injection of 60 mg/kg resveratrol 2,6,24 and 46 hours after *** 48 hours after injury,their neurological function was assessed using a modified Garcia *** edema was measured by the wet-dry *** apoptosis in the prefrontal cortex was detected by terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling *** of reactive oxygen species and malondialdehyde in the prefrontal cortex were determined by ***,glucose-regulated protein 78,nuclear factor-erythroid2-related factor 2 and heme oxygenase-1 mRNA expression levels in the prefrontal cortex were measured by reverse transcription polymerase chain *** necrosis factor-alpha content in the prefrontal cortex was detected by enzyme linked immunosorbent *** staining was used to detect the number of positive cells of nuclear factor-erythroid 2-related factor 2,heme oxygenase 1,glucose-regulated protein 78,CHOP and glial fibrillary acidic *** blot assay was utilized to analyze the expression levels of nuclear factor-erythroid 2-related factor 2,heme oxygenase 1,glucose-regulated protein 78 and CHOP protein expression levels in the prefrontal *** results showed that resveratrol treatment markedly alleviated neurological deficits and brain edema in experimental subarachnoid hemorrhage rats,and reduced neuronal apoptosis in the prefrontal *** reduced the levels of reactive oxygen species and malondialdehyde,and increased the expression of nuclear factor-erythroid 2-related factor 2,heme oxygenase-1 mRNA

关键词： nerve regeneration resveratrol oxidative stress endoplasmic reticulum stress neuroinflammation subarachnoid hemorrhage nuclear factor-erythroid 2-related factor 2 heme oxygenase-1 glucose-regulated protein 78 neural regeneration

Fluorescence imaging of Cu(Ⅰ) in endoplasmic reticulum of live cells and tissue

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Science China Chemistry 2019年第7期62卷 887-888页

作者： Xiaowen Yan X. Chris Le Key Laboratory of Spectrochemical Analysis and Instrumentation Ministry of Education Department of Chemistry College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 China Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and Pathology Faculty of Medicine and Dentistry University of Alberta Edmonton AB T6G 2G3 Canada

Copper (Cu) is an essential element to living organisms. The redox activity of Cu gives rise to redox cycling reactions between Cu^2+ and Cu^+. Organisms harness this redox cap? ability for their biological functions by tightly regulating copper homeostasis in the processes of cellular uptake, intracellular transport, protein loading and storage [1].

关键词： endoplasmic reticulum Copper (Cu) living organisms

New insights into the role of the endoplasmic reticulum in microglia

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Neural Regeneration Research 2024年第7期19卷 1397-1398页

作者： Veronika E.Neubrand M.Rosario Sepúlveda Department of Cell Biology Faculty of SciencesUniversity of GranadaGranadaSpain

Microglial cells are the only resident immune cells in the central nervous system and constitute its frontline *** are extremely reactive against infections,trauma,or toxins,but are also responsible for mediating inflammation,taking part in the pathogenic course of many neuropathologies(Sierra et al.,2019).Cell-specific staining,ultrastructural analysis by transmission electron microscopy(TEM),or two-photonmicroscopy imaging have been relevant for the characterization of microglia as well as their cell-cell interactions。

关键词： inflammation reticulum

Pollen Typhae Total Flavone Inhibits Endoplasmic reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway

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Chinese Journal of Integrative Medicine 2019年第8期25卷 604-612页

作者： CHEN Ming-tai HUANG Ruo-lan OU Li-jun CHEN Ying-nan MEN Ling CHANG Xiao WANG Ling YANG Yu-zhu ZHANG Zhong Cardiovascular Department Shenzhen Traditional Chinese Medicine Hospital Guangzhou University of Traditional Chinese Medicine

Objective: To test the hypothesis that the inhibition of endoplasmic reticulum(ER) stress-induced apoptosis in oxidized low-density lipoproteins(ox-LDL)-induced human aortic-vascular smooth muscle cells(HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase(PERK)-eukaryotic translation initiation factor 2α(e IF2α)-activating transcription factor 4(ATF4)-CCAAT/enhancer binding protein homologous protein(CHOP) signaling pathway by Pollen Typhae total flavone(PTF). Methods: Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group(70 μg/m L high ox-LDL), an HPTF group(70 μg/m L high ox-LDL+500 μg/m L PTF), an MPTF group(70 μg/m L high ox-LDL+250 μg/m L PTF), and a LPTF group(70 μg/m L high ox-LDL+100 μg/m L PTF) in the first part;and a normal control group, an ox-LDL group(70 μg/mL high ox-LDL), an MPTF group(70 μg/m L high ox-LDL+250 μg/m L PTF), a sh RNA group(transducted with PERK shRNA lentiviral particles), a scramble shRNA group(transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group(250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group(70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their m RNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was applied to test cel viability, and the level of apoptosis was monitored by flow cytometry. Results: The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and sh RNA groups. Moreover, the ox-LDL group had increased protein and m RNA levels of binding immunoglobulin protein and ER-associated

关键词： Pollen Typhae total flavone endoplasmic reticulum stress protein kinase RNA-like endoplasmic reticulum kinase-eukaryotic translation initiation factor 2a -activating transcription factor 4-CCAAT/enhancer binding protein homologous protein pathway apoptosis vulnerable atherosclerotic plaque

Prion Protein Protects Cancer Cells against Endoplasmic reticulum Stress Induced Apoptosis

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Virologica Sinica 2019年第2期34卷 222-234页

作者： Zhenxing Gao Min Peng Liang Chen Xiaowen Yang Huan Li Run Shi Guiru Wu Lili Cai Qibin Song Chaoyang Li State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China Department of Oncology Renmin Hospital of Wuhan University Wuhan 430060 China Department of the First Abdominal Surgery Jiangxi Tumor Hospital Nanchang 330029 China

Unfolded protein response(UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum(ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein(PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether underglycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A(BFA), thapsigargin(Thps), and tunicamycin(TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA,but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment.

关键词： Endoplasmic reticulum stress Brefeldin A (BFA) Prion protein (PrP)- Glycosylation Apoptosis

Induction of Endoplasmic reticulum Stress by Cadmium and Its Regulation on Nrf2 Signaling Pathway in Kidneys of Rats

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Biomedical and Environmental Sciences 2019年第1期32卷 1-10页

作者： CHEN Zhi Jian CHEN Jia Xing WU Li Kang LI Bi Yun TIAN Ya Feng XIAN Min HUANG Zi Pei YU Ri An School of Public Health Guangdong Pharmaceutical University Bao'an Center for Disease Control and Prevention of Shenzhen

Objective This study was conducted to investigate the regulation of endoplasmic reticulum stress on Nrf2 signaling pathway in the kidneys of rats. Methods Rats were divided into twelve groups of six animals each. Some groups were pre-administered with bacitracin or tauroursodeoxycholic acid(TUDCA), and all of them were treated with 5-20 μmol/kg cadmium(Cd) for 48 h. The oxidative stress levels were analyzed using kits. The mRNA and protein expression levels of endoplasmic reticulum stress-related factors and Nrf2 signaling pathway-related factors were determined using RT-PCR and western blot. Results Cd exposure resulted in oxidative stress in the kidneys of rats and upregulated the expression of endoplasmic reticulum stress(ERS)-related factors and Nrf2 signaling pathway-related factors, especially at doses of 10 and 20 μmol/kg Cd, and the expression changes were particularly obvious. Moreover, after pretreatment with bacitracin, Cd upregulated the expression of ERS-related factors to a certain extent and, at higher doses, increased the mRNA expression of Nrf2. After pretreatment with TUDCA, Cd reduced the level of ERS to a certain extent; however, at these doses, there were no significant changes in the expression of Nrf2. Conclusion Cadmium can result in ERS and oxidative stress in the kidneys of rats, activate Nrf2, and upregulate the transcriptional expression of phase II detoxification enzymes under these experimental conditions. ERS has a positive regulation effect on Nrf2 signaling pathway but has little effect on the negative regulation of Nrf2 signaling pathway in cadmium toxicity.

关键词： Cadmium Endoplasmic reticulum stress PERK Nrf2 Kidney Rat

Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

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International Journal of Oral Science 2021年第1期13卷 108-116页

作者： Wen Chen Chenzhou Wu Yafei Chen Yuhao Guo Ling Qiu Zhe Liu Haibin Sun Siyu Chen Zijian An Zhuoyuan Zhang Yi Li Longjiang Li State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Head and Neck Oncology West China Hospital of StomatologySichuan UniversityChengduChina Department of Oral and Maxillofacial-Head and Neck Oncology Capital Medical University School of StomatologyBeijingChina

C18 ceramide plays an important role in the occurrence and development of oral squamous cell ***,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma is still *** aim of our study was to investigate the relationship between ceramide synthase 1 and oral *** this study,we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell *** a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide,ceramide synthase 1 knockout was associated with the severity of oral malignant *** studies showed significant upregulation of PCNA,MMP2,MMP9,and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic *** addition,ceramide synthase 1 knockdown promoted cell proliferation,migration,and invasion in *** of CERS1 obtained the opposite *** synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA *** transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional *** addition,mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin *** together,our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

关键词： endoplasmic cancer reticulum

A ratiometric fluorescent sensor for tracking Cu(Ⅰ) fluctuation in endoplasmic reticulum

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Science China Chemistry 2019年第4期62卷 465-474页

作者： Jungu Guo Hao Yuan Yuncong Chen Zhongyan Chen Menglong Zhao Liang Zou Yi Liu Zhipeng Liu Qiang Zhao Zijian Guo Weijiang He State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringNanjing University Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors Institute of Advanced Materials(IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM)Nanjing University of Posts & Telecommunications Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM) Nanjing Tech University (NanjingTech)

A two-photon ratiometric fluorescent sensor for Cu^+ in endoplasmic reticulum(ER), CNSB, was developed via coumarin/ASBD integration based on FRET mechanism. In solution, CNSB shows reversible, highly-specific ratiometric response to Cu^+ .Moreover, CNSB exhibits suitable K_d value, suggesting the possibility of detecting Cu^+ in the living cells. The probe can enter the MCF-7 cells easily and specifically locates in the ER. The highly specific ratiometric response of CNSB toward Cu^+ in MCF-7 cells provides the sensor the capacity to visualize both exogenous and endogenous Cu^+ in the ER via fluorescence ***, CNSB was utilized to detect the fluctuation and distribution of Cu^+ under ER stress in MCF-7 cells, which confirmed directly the relationship between Cu^+ enhancement and ER stress. Meanwhile, the two-photon ability of coumarin facilitated the sensor to visualize Cu^+ fluctuation via two-photon fluorescence imaging. In addition, the spatial distribution of Cu^+ in the heart slice of the 14-day-old rat was demonstrated using CNSB. This study demonstrates the promising potential of CNSB in clarifying the Cu^+ -dependent signaling in the ER stress-related diseases.

关键词： Cu(Ⅰ) ratiometric two-photon endoplasmic reticulum-targeting endoplasmic reticulum stress heart tissue slice

GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2019年第7期14卷 1221-1229页

作者： Zi-Wei Han Yue-Chen Chang Ying Zhou Hang Zhang Long Chen Yang Zhang Jun-Qiang Si Li Li Department of Physiology Medical College of Shihezi University Key Laboratory of Xinjiang Endemic and Ethnic Disease Shihezi University School of Medicine Affiliated Teng Zhou Central People's Hospital Jining Medical University Department of Physiology Jiaxing College of Medicine

Studies have confirmed a strong association between activation of the endoplasmic reticulum stress pathway and cerebral ischemia/reperfusion(I/R) *** this study,three key proteins in the endoplasmic reticulum stress pathway(glucose-regulated protein 78,caspase-12,and C/EBP homologous protein) were selected to examine the potential mechanism of endoplasmic reticulum stress in the neuroprotective effect of G protein-coupled estrogen *** Sprague-Dawley rats received ovariectomy(OVX),and then cerebral I/R rat models(OVX+ I/R) were established by middle cerebral artery *** after I/R,rat models were injected with 100 μg/kg E2(OVX + I/R +E2),or 100 μg/kg G protein-coupled estrogen receptor agonist G1(OVX + I/R + G1) in the lateral *** scoring was used to detect neurobehavioral changes in each *** volumes were measured by 2,3,5-triphenyltetrazolium chloride *** changes in neurons were observed by Nissl *** dexynucleotidyl transferase-mediated nick end-labeling staining revealed that compared with the OVX + I/R group,neurological function was remarkably improved,infarct volume was reduced,number of normal Nissl bodies was dramatically increased,and number of apoptotic neurons in the hippocampus was decreased after E2 and G1 *** detect the expression and distribution of endoplasmic reticulum stress-related proteins in the endoplasmic reticulum,caspase-12 distribution and expression were detected by immunofluorescence,and mRNA and protein levels of glucose-regulated protein 78,caspase-12,and C/EBP homologous protein were determined by polymerase chain reaction and western blot *** results showed that compared with the OVX+ I/R group,E2 and G1 treatment obviously decreased mRNA and protein expression levels of glucose-regulated protein 78,C/EBP homologous protein,and ***,the G protein-coupled estrogen receptor antagonist G15(OVX + I/R + E2 + G15) could eli

关键词： nerve regeneration cerebral ischemia/reperfusion injury estrogen G protein-coupled estrogen receptor G1 G15 endoplasmic reticulum stress glucose-regulated protein 78 caspase-12 C/EBP homologous protein neuronal apoptosis neural regeneration