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Presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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Neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan JoséPérez-Moreno Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HSP)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower limbs.Pat ients can also experience peripheral neuropathy,cognitive impairment,and other neurological symptoms.To date,more than 80 genes have been implicated in HSP,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(Parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSP.

关键词： reticulum endoplasmic

Janus-faced Mitofusin 2 (MFN2): mitochondria-endoplasmic reticulum shaping and tethering functions unveiled

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Signal Transduction and Targeted Therapy 2024年第2期9卷 341-342页

作者： Camilla Aurora Franchino Elisa Motori Matteo Bergami Institute for Biochemistry University of Cologne50674 CologneGermany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases(CECAD) Faculty of Medicine and University Hospital CologneUniversity of Cologne50931 CologneGermany Center for Molecular Medicine 50931 CologneGermany

In a recently published study in Science,Naòn et al.report two uncharacterized splice variants of Mitofusin 2(MFN2)that specifically shape and tether the endoplasmic reticulum(ER)to mitochondria.1 This work sheds new light on the pleiotropic effects previously ascribed to MFN2 loss-of-function mutations,and has important implications for associated metabolic and neurological diseases.

关键词： MFN2 reticulum

Probing the endoplasmic reticulummitochondria interaction in Alzheimer's disease:searching far and wide

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Neural Regeneration Research 2024年第10期19卷 2103-2104页

作者： Giulia Dematteis Laura Tapella Dmitry Lim Department of Pharmaceutical Sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly

Alzheimer's disease(AD)is the most frequent,form of dementia in elderly people and is an incurable disease with an exponentially growing number of cases.Extracellular deposition of amyloid-β(Aβ)plaques and intraneur... 详细信息

关键词： Alzheimer Aβ reticulum

SUN3/4/5 proteins regulate endoplasmic reticulum tubule formation and luminal spacing in Arabidopsis

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Journal of Genetics and Genomics 2023年第5期50卷 370-373页

作者： Yong Xue Peng-Fei Jia Hong-Ju Li State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

The endoplasmic reticulum(ER)is the processing factory of secretory proteins and the largest membrane-bound organelle with multiple interactions with the other organelles.It is a dynamic network composed of two morphologically distinct domains:tubules and sheets with constant luminal spacing(Chen et al.,2012).The ER shape is generated and modified by ER shaping proteins according to the cellular and developmental context as well as in response to environmental signals(Ridge et al.,1999;Takemoto et al.,2003).Although several key regulators in ER remodeling have been identified(Sparkes et al.,2010;Chen et al.,2011;Yokota et al.,2011;Lee et al.,2013;O’Sullivan et al.,2013;Kriechbaumer et al.,2018;Kriechbaumer and Brandizzi,2020),how the morphologically distinct domains are established and maintained is still unclear.Additionally,the ER network is quite dynamic,but the luminal space of the ER sheets is approximately constant.In the metazoan,the ER spacing is maintained by the coiled-coil protein Climp 63(Shibata et al.,2010).Though it is postulated that plants and yeasts lack the Climp63 homolog,thus exhibiting a narrower ER luminal space than the animal cells,it is still unclear how the“basal space”is maintained in plants and yeasts.In our recent study on the ER sorting of receptor kinases,we noticed the narrower ER lumen in sun3/4/5 mutant(Xue et al.,2022),which raises the possibility that the ER-localized SUN proteins may also function in the ER structure.

关键词： luminal reticulum spacing

Tetrahydropalmatine attenuates liver fibrosis by suppressing endoplasmic reticulum stress in hepatic stellate cells

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Chinese Medical Journal 2022年第5期135卷 628-630页

作者： Yuanyuan Xuan Shiyun Chen Xin Ding Lexun Wang Shengwen Li Guizhi Yang Tian Lan Institute of Chinese Medicine Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China Clinical Medicine Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine GuangzhouGuangdong 510006China

To the Editor: Liver fibrosis was characterized by the activation of hepatic stellate cells (HSCs) and extracellular matrix deposition. The pathogenesis of liver fibrosis involved many aspects. Studies have found that endoplasmic reticulum stress (ERS) in HSCs could lead to HSC activation and aggravate liver fibrosis.[1] Although liver fibrosis has been extensively studied, effective anti-fibrotic drugs are lacking at present. Tetrahydropalmatine (THP) was the active ingredient of Chinese herbs Corydalis yanhusuo. Previous studies have found the hepatoprotective effect of THP. Our study aimed to investigate the effects of THP on liver fibrosis and the underlying mechanisms.

关键词： hepatic reticulum protective

Novel endogenous endoplasmic reticulum transmembrane protein SURF4 suppresses cell death by negatively regulating the STING-STAT6 axis inmyeloid leukemia

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Cancer Communications 2023年第3期43卷 395-399页

作者： Jayoung Kim Hansong Lee Chae Mi Hong Ji Ho Nam Hye Ju Yeo Woo Hyun Cho Hyung-Sik Kim Changwan Hong Yun Hak Kim Dongjun Lee Department of Convergence Medicine School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Biomedical Informatics School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Radiation Oncology School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Division of Allergy Pulmonaryand Critical Care MedicineDepartment of Internal MedicinePusan National University Yangsan HospitalYangsanGyeongsangnam-do 50612Republic of Korea Department of Oral Pathology Dental and Life Science InstituteSchool of DentistryPusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Anatomy School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea

Dear Editor,Myeloid differentiation was shown to be associated with reduced leukemic cell burden and leukemia-initiating cells and improved survival[1].Reactive oxygen species(ROS)are associated with leukemia and can induce endoplasmic reticulum(ER)stress.ER stress induces several mechanisms,including cell death[2].The stimulator of interferon genes(STING)is also an ER transmembrane protein and promotes anti-tumor immunity by linking innate and adaptive immunity[3].Signal transducer and activator of transcription 6(STAT6)plays a prominent role in adaptive immunity by transducing signals fromextracellular cytokines and inducing apoptosis in cancer cells[4].

关键词： STAT6 immunity reticulum

Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress

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Journal of Integrative Medicine 2019年第3期17卷 205-212页

作者： Fang-yuan Wang Jian Jia Huan-huan Song Cheng-ming Jia Chang-bo Chen Jing Ma Department of Traditional Chinese Medicine Army Medical Center in Traditional Chinese MedicineXijing HospitalForth Military Medical University

Objective: To investigate the protective effect and underlying mechanism(s) of icariin(ICA) in preventing hydrogen peroxide(H_2O_2)-induced vascular endothelial cell injury via endoplasmic reticulum stress(ERS).Methods: To study the effects of ICA on H_2O_2-induced damage, we used the cell counting kit-8 assay to detect cell viability and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay to determine cell adhesion and apoptosis, respectively. Spectrophotometry and enzyme-linked immunosorbent assay were used to measure the expression levels of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px). Subsequently, glucose-regulated protein 78(GRP78), activating transcription factor-4(ATF4) and eukaryotic initiation factor-2 a(eIF2 a) were detected using Western blotting.Results: In human umbilical vein endothelial cells, different concentrations of ICA exhibited multiple effects, including reduced H_2O_2 damage, improved cell viability and adhesion, reduced cell apoptosis and increased SOD and GSH-Px activity. Among the ICA concentrations used, only the H_2O_2+ 100 lmol/L ICA group had significant differences compared to the H_2O_2 group. ERS activators H_2O_2 and DL-dithiothreitol(DTT) significantly increased GRP78, ATF4 and eIF2 a expressions, decreased cell activity and reduced SOD and GSH-Px activity. In contrast, the H_2O_2+ 100 lmol/L ICA and H_2O_2+ 100 lmol/L ICA + DTT groups had significant inhibitory effects on the expressions of GRP78,ATF4 and eIF2 a proteins, showing enhanced cell viability and SOD and GSH-Px activity.Conclusion: The results showed the dose-dependent effects of ICA against H_2O_2-induced injury in vascular endothelial cells. The inhibition of GRP78, ATF4 and eIF2 a protein expressions in the ERS, and the subsequent alleviation of oxidative stress damage, might be the molecular mechanism.

关键词： Icariin Endoplasmic reticulum stress Human umbilical vein endothelial cells Oxidative stress

Isorhamnetin protects zearalenone-induced damage via the PI3K/Akt signaling pathway in porcine ovarian granulosa cells

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Animal Nutrition 2022年第4期11卷 381-390页

作者： Xiaoya Li Huali Chen Zelin Zhang Jiaxin Duan Rongmao Hua Xiaodi Li Li Yang Jianyong Cheng Qingwang Li College of Animal Science and Technology Northwest A&F UniversityYangling712100China School of Life Science and Engineering Southwest University of Science and TechnologyMianyang 621000China College of Basic Medicine Hebei University of Chinese MedicineShijiazhuang050000China

Zearalenone(ZEA)is widely derived from moldy cereal grain,which has adverse effects on animal reproduction.In particular,pigs are more sensitive to ZEA-induced toxicity than other animals.Isorhamnetin has extensive pharmacological activity.However,the role of isorhamnetin in ZEA-induced cytotoxicity remains unclear.This study was designed to investigate the therapeutic effect of isorhamnetin on ZEA-induced damage in porcine ovarian granulosa cells and elucidate its molecular mechanism.Two experiments were conducted,where a minimum of 3 biological replicates were used for each treatment.In Exp.1,ovarian granulosa cells were treated with different concentrations of isorhamnetin(1,5,10,20 and 30μmol/L)and ZEA(0,10,30,60,90 and 120μmol/L)for 24 h.Our results indicated that 60μmol/L ZEA(half-maximal inhibitory concentration value)and 20μmol/L isorhamnetin(the most effective concentration against ZEA-induced cytotoxicity)were optimum concentrations.In Exp.2,ovarian granulosa cells were treated with isorhamnetin(20μmol/L)for 2 h,before treatment with ZEA(60μmol/L)for 24 h.Apoptosis,endoplasmic reticulum stress,oxidative stress,proliferation and hormone secretion of ovarian granulosa cells were detected.Our findings showed that isorhamnetin suppressed(Preticulum stress.Furthermore,isorhamnetin prevented(P<0.05)ZEA-induced oxidative stress via the mitogen-activated protein kinase(P38)signaling pathway.Mechanistically,isorhamnetin stimulated(P<0.05)the expression of proliferating cell nuclear antigen(PCNA)and cyclin D,thereby increasing the ratio of S phase cells in response to ZEAinduced apoptosis via phosphatidylinosi

关键词： Zearalenone Isorhamnetin Ovarian granulosa cell Apoptosis Endoplasmic reticulum stress Oxidative stress

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4629-4668页

作者： Xingyi Chen Chaoran Shi Meihui He Siqi Xiong Xiaobo Xia Eye Center of Xiangya Hospital Central South University410008 ChangshaHunanChina Hunan Key Laboratory of Ophthalmology Central South University410008 ChangshaChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaChina

The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.

关键词： reticulum homeostasis stasis