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Metabolism of minor isoforms of prion proteins Cytosolic prion protein and transmembrane prion protein

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Neural Regeneration Research 2013年第30期8卷 2868-2878页

作者： Zhiqi Song Deming Zhao Lifeng Yang State Key laboratory for Agrobiotechnology National Animal Transmissible Spongiform Encephalopathy Laboratory College of Veterinary Medicine China Agricultural University

transmissible spongiform encephalopathy or prion disease is triggered by the conversion from cellular prion protein to pathogenic prion protein. Growing evidence has concentrated on prion protein configuration changes and their correlation with prion disease transmissibility and patho- genicity. In vivo and in vitro studies have shown that several cytosolic forms of prion protein with specific topological structure can destroy intracellular stability and contribute to prion protein pathogenicity. In this study, the latest molecular chaperone system associated with endoplasmic re- ticulum-associated protein degradation, the endoplasmic reticulum resident protein quality-control system and the ubiquitination proteasome system, is outlined. The molecular chaperone system directly correlates with the prion protein degradation pathway. Understanding the molecular mechanisms will help provide a fascinating avenue for further investigations on prion disease treatment and prion protein-induced neurodegenerative diseases.

关键词： neural regeneration neurodegeneration prion protein cytosolic form of prion protein transmem-brane form of prion protein metabolism protein degeneration ubiquitination molecular chaperone molecular mechanism neuroregeneration

All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets

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Journal of animal Science and Biotechnology 2024年第3期15卷 1131-1144页

作者： Junning Pu Daiwen Chen Gang Tian Jun He Ping Zheng Zhiqing Huang Xiangbing Mao Jie Yu Yuheng Luo Junqiu Luo Hui Yan Aimin Wu Bing Yu Institute of animal Nutrition Sichuan Agricultural UniversityChengdu 611130SichuanPeople’s Republic of China Key laboratory of animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan Province611130 ChengduSichuanPeople’s Republic of China

Background transmissible gastroenteritis virus(TGEV)is one of the main pathogens causing severe diarrhea of *** pathogenesis of TGEV is closely related to intestinal ***-trans retinoic acid(ATRA)is the main active metabolite of vitamin A,which has immunomodulatory and anti-inflammatory ***,it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in *** study aimed to investigate the effects of ATRA on growth performance,diarrhea,intestinal inflammation and intesti-nal barrier integrity of TGEV-challenged *** In a 19-d study,32 weaned piglets were randomly divided into 4 treatments:Control group(basal diet),TGEV group(basal diet+TGEV challenge),TGEV+ATRA5 group(basal diet+5 mg/d ATRA+TGEV challenge)and TGEV+ATRA15 group(basal diet+15 mg/d ATRA+TGEV challenge).On d 14,piglets were orally administered TGEV or the sterile *** Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV(P<0.05).Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase(DAO)activ-ity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV,and maintained intestinal barrier integrity(P<0.05).Meanwhile,5 mg/d ATRA feeding increased the sucrase activity and the expres-sions of nutrient transporter related genes(GLUT2 and SLC7A1)in jejunal mucosa of TGEV-challenged piglets(P<0.05).Furthermore,5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibit-ing the release of interleukin(IL)-1β,IL-8 and tumor necrosis factor-α(TNF-α),and promoting the secretion of IL-10 and secretory immunoglobulin A(sIgA)(P<0.05).Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes(TLR3,TLR4,RIG-I,MyD88,TRIF and MAVS)and the phosphorylation level of nuclear factor-κB-p65(NF-κB p65),and

关键词： All-trans retinoic acid Inflammation Intestinal barrier Piglets transmissible gastroenteritis virus

Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication

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Journal of Integrative Agriculture 2024年第3期23卷 988-1005页

作者： Qi Gao Yongzhi Feng Ting Gong Dongdong Wu Xiaoyu Zheng Yizhuo Luo Yunlong Yang Zebu Song Lang Gong Guihong Zhang Guangdong Provincial Key laboratory of Zoonosis Prevention and Control College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642China Maoming Branch Guangdong Laboratory for Lingnan Modern AgricultureMaoming 525000China Key laboratory of animal Vaccine Development Ministry of Agriculture and Rural AffairsGuangzhou 510000China Guangdong laboratory for Lingnan Modern Agriculture Guangzhou 510642China

Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.

关键词： porcine enteric alphacoronavirus NF-κB inflammatory pathway lipid droplet metformin hydrochloride

Kallikrein 12 regulates innate resistance of murine macrophages against Mycobacterium bovis infection by modulating autophagy and apoptosis

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Kallikrein 12 regulates innate resistance of murine macropha...

Microrna 27a-3p regulates antimicrobial responses of Murine Macrophages infected by Mycobacterium avium subspecies paratuberculosis by Targeting interleukin-10 and TgF-β-activated Protein Kinase 1 Binding Protein 2

中国畜牧兽医学会兽医病理学分会第二十五次学术交流会、中国病理生理学会动物病理学专业委员会第二十四次学术研讨会、中国实验动物学会实验病理学专业委员会第四次学术研讨会、中国兽医病理学家第四次研讨会

作者： Naveed Sabir Tariq Hussain Yi Liao Jie Wang Yinjuan Song Muhammad Shahid Guangyu Cheng Mazhar Hussain Mangi Jiao Yao Lifeng Yang Deming Zhao Xiangmei Zhou national animal transmissible spongiform encephalopathy laboratory College of Veterinary Medicine China Agricultural University

(Objective)SeseC1411 as a novel protective antigen of Streptococcus equi ssp. Zooepidemicus（SEZ）, although its protective efficacy remained to be evaluated.（Method）In this study,purified recombinant SeseC1411 protein emulsified in adjuvant,then immunizing mice,after ten days of the secondary immunization,we collected the serum for antibody titers determination,and the serum was used in immunofluorescence microscopy analysis also flow cytometry *** measure the expression of SeseC1411 through quantitative real-time PCR and verified anti-SeseC1411 protective of mice against SEZ lethal challenge.（Result） Our study found that SeseC1441 could induce high titer of IgG antibody in mice.

关键词： Mycobacterium bovis murine macrophages Kallikrein12 autophagy apoptosis cytokines

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Microrna 27a-3p regulates antimicrobial responses of Murine ...

Influence of PrP 106―126 on expression of laminin and fibronectin in astrocyte

中国畜牧兽医学会兽医病理学分会第二十四次学术研讨会、中国病理生理学会动物病理生理学专业委员会第二十三次学术研讨会、中国实验动物学会实验病理学专业委员会第三次学术研讨会、中国兽医病理学家第三次学术研讨会

作者： Tariq Hussain Deming Zhao Syed Zahid Ali Shah Jie Wang Ruichao Yue Yi Liao Naveed Sabir Lifeng Yang Xiangmei Zhou national animal transmissible spongiform encephalopathy laboratory College of Veterinary Medicine China Agricultural University

Mycobacterium avium subspecies paratuberculosis(MAP) persistently survive and replicate in macrophages by adopting various strategies to subvert host immune response. Interleukin-10(IL-10) upregulated via MAPK-p38 signaling cascade is a critical step for MAP survival and pathogenesis within the host cell. In the current study, we found that miR-27 a expression is downregulated during MAP infection both in vivo and in vitro. We observed that overexpression of miR-27 a inhibited MAP induced IL-10 production in macrophages and upregulated proinflammatory cytokines, while miR-27 a inhibitor counteracted these effects. Luciferase reporter assay results revealed that IL-10 and TAB2 are potential targets of miR-27 a. Furthermore, overexpression of miR-27 a significantly inhibited the intracellular survival of MAP in infected macrophages. Our data shows that miR-27 a augments antimicrobial activities of macrophages and inhibits the expression of IL-10, demonstrating that miR-27 a regulates protective innate immune responses during MAP infection and can be exploited as a novel therapeutic target in the control of intracellular pathogens, including MAP.

关键词： Mycobacterium avium subspecies paratuberculosis (MAP) MicroRNAs (miRNAs) miR-27a Mitogen activated protein kinase p38 (MAPK-p38) TAK1 binding protein 2 (TAB2) interleukin-10 (IL-10)

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Chinese Science Bulletin 2008年第14期53卷 2160-2164页

作者： LI YuRong GUAN LeLuo YANG JianMin ZHOU XiangMei YIN XiaoMin ZHAO DeMing Nattional animal transmissible spongiform encephalopathy laboratory College of Veterinary Medicine China Agricultural University Beijing 100094 China Department of animal Science and Technology Hebei Agricultural University Baoding 071001 China Department of Agricultural Food and Nutritional Science University of Alberta Edmonton Alberta T6G2P5 Canada

Astrogliosis is a hallmark of prion disease, but the metabolic alterations of astrocytes remain poorly documented. A synthetic peptide corresponding to amino acid 106―126 of the human prion protein (PrP) has been shown to be toxic to neurons. In this study, the effects of PrP 106―126 on astrocytes were investigated in vitro. The proliferation of astrocytes was significantly (P < 0.05) increased when grown in media conditioned with PrP 106―126 (80 μmol/L) from microglia. The expression of laminin (LN) and fibronectin (FN) was examined at both mRNA and protein levels. The results showed that ex- posure of astrocytes to PrP 106―126 enhanced the expression of LN and FN. The increase of FN in astrocyte cultures required cytokines previously released by activated microglia. This study reveals the expression of LN and FN affected by PrP106―126.

关键词：纤连蛋白 PrP 106-126 星形胶质细胞小胶质

PrP 106-126 Altered PrP mRNA Gene Expression in Mouse Microglia BV-2 Cells

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Virologica Sinica 2010年第6期25卷 440-444页

作者： Yu BAI Yu-rong LI Gui-hua WANG Xiang-mei ZHOU De-ming ZHAO The state key Lab of Agrobiotechnology national animal transmissible spongiform Eneephalopathy laboratory College of Veterinary Medicine China Agricultural University Beo＇ing 100193 China Department of animal Science and Technology Agricultural University of Hebei Baoding 071001 China Department of animal Science and Technology Agricultural University of Shandong Taian 271018 China

Prion diseases are infectious and fatal neurodegenerative *** pathogenic agent is an abnormal prion protein *** activation in the centre nervous system is a characteristic feature of prion *** this study,we examined the effect of PrP 106-126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative *** mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106-126,with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred *** results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106-126,and indicate that microglial cells might play a critical role in prion pathogenesis.

关键词： Prion PrP106-126 PrP mRNA Mouse microglia BV-2 Cells

Parkin prevents Prp106-126 peptide induce toxicity in N2a cells

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Parkin prevents Prp106-126 peptide induce toxicity in N2a ce...

Emergence and prevalence of naturally occurring lower virulent African swine fever viruses in domestic pigs in China in 2020

中国畜牧兽医学会兽医病理学分会第二十一次学术研讨会暨中国病理生理学会动物病理生理专业委员会第二十次学术研讨会

作者： Sher Hayat Khan Zhou Xiangmei Zhao Deming Yang Lifeng national spongiform encephalopathy Lab College of Veterinary Medicine China Agricultural University

Introduction:transmissible spongiform encephalopathy’s(TSEs)are a group of fatal neurodegenerative diseases of animals and *** diseases are caused by the deposition of an abnormal iso-form of prion protein(Pr PSc).Protein aggregation,misfolding and toxicity in the brain are the major causes of neuronal *** Ubiquitin Proteosome System(UPS)is the major pathway that targets defective

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Science China(Life Sciences) 2021年第5期64卷 752-765页

作者： Encheng Sun Zhenjiang Zhang Zilong Wang Xijun He Xianfeng Zhang Lulu Wang Wenqing Wang Lianyu Huang Fei Xi Haoyue Huangfu Ghebremedhin Tsegay Hong Huo Jianhong Sun Zhijun Tian Wei Xia Xuewu Yu Fang Li Renqiang Liu Yuntao Guan Dongming Zhao Zhigao Bu State Key laboratory of Veterinary Biotechnology National High Containment Facilities for Animal Diseases Control and PreventionHarbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of animal Science and Technology Inner Mongolia University for NationalitiesTongliao 028000China

African swine fever virus(ASFV)has been circulating in China for more than two years,and it is not clear whether the biological properties of the virus have ***,we report on our surveillance of ASFVs in seven provinces of China,from June to December,2020.A total of 22 viruses were isolated and characterized as genotype II ASFVs,with mutations,deletions,insertions,or short-fragment replacement occurring in all isolates compared with Pig/HLJ/2018(HLJ/18),the earliest isolate in *** isolates had four different types of natural mutations or deletion in the EP402R gene and displayed a nonhemadsorbing(non-HAD)*** isolates were tested for virulence in pigs;two were found to be as highly lethal as HLJ/***,two non-HAD isolates showed lower virulence but were highly transmissible;infection with 106 TCID50 dose was partially lethal and caused acute or sub-acute disease,whereas 103 TCID50 dose caused non-lethal,sub-acute or chronic disease,and persistent *** emergence of lower virulent natural mutants brings greater difficulty to the early diagnosis of ASF and creates new challenges for ASFV control.

关键词： African swine fever virus natural mutant non-hemadsorbing lower virulent