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A pedigree with retinitis pigmentosa and its concomitant ophthalmic diseases

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International Journal of Ophthalmology(English edition) 2023年第12期16卷 1962-1970页

作者： Hong-Dou Luo Shao-Nan Pei Ai-Jia Wang Xue-Qing Yu Hai-Jian Hu Ling Zeng Fei-Fei Wang Ming Jin Xu Zhang Affiliated Eye Hospital of Nanchang University Jiangxi Research Institute of Ophthalmology&Visual Science/Jiangxi Provincial Key Laboratory for OphthalmologyNanchang 330006Jiangxi ProvinceChina

AIM:To characterize the ophthalmic clinical phenotype of a family with retinitis pigmentosa(RP)and closed-angle glaucoma and to detect pathogenic genes and mutation sites causing RP in this family.METHODS:Ophthalmic clinic performance was examined in detail in 8 enrolled family members.Genomic DNA was extracted from the peripheral blood of 4 family members for whole-exome sequencing(WES)to select potential genetic mutations whose structures were identified by bioinformatics analysis.Then,Sanger sequencing was used in 12 family members and control group members to validate and confirm the disease-causing mutation loci,and we analyzed the genotype-phenotype relationships.RESULTS:The known c.512C>T(p.P171L)mutation in the rhodopsin(rho)gene was only found in afflicted family members and was confirmed by WES and Sanger sequencing as the pathogenic mutation in this family.In addition to being diagnosed with RP,family member III:4 was found to have bilateral closed-angle glaucoma,high myopia,and concurrent cataracts,and family members II:2 and II:4 had pathological changes of anterior chamber angle narrowing.Family members IV:3 and IV:4 were found to have retinoschisis.CONCLUSION:Glaucoma and related pathological changes,such as retinoschisis,in family members are preliminarily considered RP complications caused by rho mutation.

关键词： retinitis pigmentosa glaucoma wholeexome sequencing rho

Roles of rho/Rock Signaling Pathway in Silica-induced Epithelial-mesenchymal Transition in Human Bronchial Epithelial Cells

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Biomedical and Environmental Sciences 2013年第7期26卷 571-576页

作者： HU Yong Bin LI Xiang LIANG Guan Nan DENG Zheng Hao JIANG Hai Ying ZHOU Jian Hua Department of Pathology Xiangya Basic Medical School Central South University

Objective To investigate the roles of rho/Rock signaling pathway in silica-induced Epithelial-mesenchymal transition （EMT） in human bronchial epithelial cells （BEC） in vitro. Methods Human BEC were incubated with silica with various concentrations for indicated times. Cell viability was assayed by MTT test. Morphologic Changes were observed by microscope. Mesenchymal marker a-smooth muscle actin （a-SMA）, vimentin （Vim）, and epithelial marker E-cadherin （E-cad） were analyzed by Western Blot. The pull-down assay was used to measure rho activity. In the prevention experiments, the specific inhibitor for rho effector ROCK （Y27632） was used to inhibit the activity of rho. Results Human BEC stimulated with silica were converted from a ＂cobblestone＂ epithelial structure into an elongated fibroblast-like shape structure. Incubation of human BEC with silica induced de novo expression of a-SMA and Vim, and loss of E-cad. Also, silica treatment resulted in rho activation in human BEC. Y27632 up-regulated the E-cad expression but attenuated a-SMA and Vim expression in silica-stimulated cells. Conclusion The activation of rho/ROCK signaling pathways is most likely involved in Silica-induced EMT in human bronchial epithelial cells.

关键词： Silica Bronchial epithelial cell Epithelial-to-mesenchymal transition rho

Mitochondria Redistribution in Enterovirus A71 Infected Cells and Its Effect on Virus Replication

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Virologica Sinica 2019年第4期34卷 397-411页

作者： Yang Yang Haolong Cong Ning Du Xiaodong Han Lei Song Wenliang Zhang Chunrui Li Po Tien Center for Molecular Virology CAS Key Laboratory of Pathogenic Microbiology and ImmunologyInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of the Chinese Academy of Sciences Beijing 100101China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China College of Life Sciences Inner Mongolia Agriculture UniversityHohhot 010018China

Enterovirus A71(EV-A71)is one of the main causative agents of hand,foot and mouth disease(HFMD)and it also causes severe neurologic complications in infected children.The interactions between some viruses and the host mitochondria are crucial for virus replication and pathogenicity.In this study,it was observed that EV-A71 infection resulted in a perinuclear redistribution of the mitochondria.The mitochondria rearrangement was found to require the microtubule network,the dynein complex and a low cytosolic calcium concentration.Subsequently,the EV-A71 non-structural protein 2BC was identified as the viral protein capable of inducing mitochondria clustering.The protein was found localized on mitochondria and interacted with the mitochondrial rho GTPase 1(rhoT1)that is a key protein required for attachment between the mitochondria and the motor proteins,which are responsible for the control of mitochondria movement.Additionally,suppressing mitochondria clustering by treating cells with nocodazole,EHNA,thapsigargin or A23187 consistently inhibited EV?A71 replication,indicating that mitochondria recruitment played a crucial role in the EV-A71 life cycle.This study identified a novel function of the EV-A71 2BC protein and provided a potential model for the regulation of mitochondrial motility in EV-A71 infection.

关键词： Enterovirus A71(EV-A71) Mitochondria Microtubule network Calcium concentration Mitochondrial rho GTPase 1(rhoT1)

Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons

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Journal of Genetics and Genomics 2019年第2期46卷 87-96页

作者： Tao Tao Jie Sun Yajing Peng Pei Wang Xin Chen Wei Zhao Yeqiong Li Lisha Wei Wei Wang Yanyan Zheng Ye Wang Xuena Zhang Min-Sheng Zhu Model Animal Research Center State Key Laboratory of Pharmaceutical Biotechnology Department of Neurology of the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School Nanjing University

As a critical guanine nucleotide exchange factor(GEF) regulating neurite outgrowth, Trio coordinates multiple processes of cytoskeletal dynamics through activating Rac1, Cdc42 and rhoA small GTPases by two GEF domains, but the in vivo roles of these GEF domains and corresponding downstream effectors have not been determined yet. We established multiple lines of knockout mice and assessed the respective roles of Trio GEF domains and Rac1 in axon outgrowth. Knockout of total Trio in cerebellar granule neurons(CGNs) led to an impaired F-actin rearrangement of growth cone and hence a retarded neurite outgrowth. Such a retardation was reproduced by inhibition of GEF1 domain or knockdown of Cdc42 and restored apparently by introduction of active Cdc42. As Rac1 deficiency did not affect the neurite outgrowth of CGNs, we suggested that Trio GEF1-mediated Cdc42 activation was required for neurite outgrowth. We established a GEF2-knockout line with deletion of all Trio isoforms except a cerebella-specific Trio8, a short isoform of Trio without GEF2 domain, and used this line as a GEF2-deficient animal model. The GEF2-deficient CGNs had a normal neurite outgrowth but abolished Netrin-1-promoted growth, without affecting Netrin-1 induced Rac1 activation. We thus suggested that Trio GEF1-mediated Cdc42 activation rather than Rac1 activation drives the F-actin dynamics necessary for neurite outgrowth, while GEF2 functions in Netrin-1-promoted neurite elongation. Our results delineated the distinct roles of Trio GEF domains in neurite outgrowth, which is instructive to understand the pathogenesis of clinical Trio-related neurodevelopmental disorders.

关键词： Trio GEF rho GTPases Axon outgrowth Cerebellar granule neuron

Small GTPases:Structure,biological function and its interaction with nanoparticles

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Asian Journal of Pharmaceutical Sciences 2019年第1期14卷 30-39页

作者： Siyang Song Wenshu Cong Shurong Zhou Yujie Shi Wenbing Dai Hua Zhang Xueqing Wang Bing He Qiang Zhang Shenyang Pharmaceutical University No.103Wenhua RoadShenyang 110016China Peking University No.38Xueyuan RoadBeijing 100191China

Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign particles.Therefore,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical field.However,there is no review in this aspect.This review summarizes the small GTPases in terms of the structure,biological function and its interaction with nanoparticles.We briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different GTPases.These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study.This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction.It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.

关键词： Small GTPase Nanoparticles Ras Rab rho

A Zeolitic rho-type Chiral Metal-organic Framework Based on L-alanine

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Chinese Journal of Structural Chemistry 2019年第6期38卷 963-969页

作者：王宁傅红如谢涛史风月王廷一鄢立兵李飞飞 College of Chemistry and Chemical Engineering Luoyang Normal UniversityLuoyang471934China College of Chemistry and Chemical Engineering Henan Polytechnic UniversityJiaozuo 454000China Tianjin Nankai High School Tianjin 300100China

One new chiral zeolitic rAo-type metal-organic framework[Cd(L-ala)2]n(l)has been successfully synthesized based on L-alanine chiral ligand,which demonstrates the feasibility of fabricating MOF that integrates the 4-connected zeotype topology by the employment of Z-alanine.To the best of knowledge,it's the first report that metal-organic framework based on amino acid features the chiral zeolitic rho-type structure.Compound 1 was characterized by X-ray powder diffraction,elemental analysis and single-crystal X-ray diffraction.Crystal data:CbH9CdN2O4,Mr=285.55,cubic system,space group/432,a=24.0795(6),V=13961.9(10)A3,Z=48,Dc=1.630 Mg/m3,F(000)=6672,μ(MoKa)=1.865 mm-1,S=1.058,R=0.0271 and wR=0.0312 for 1870 observed reflections with I>2δ(I).The circular dichroism(CD)property of compound 1 was also investigated.

关键词： homochiral metal-organic framework rho zeolitic topology L-alanine

Function of rho GTPase Activating Protein 11A in Tumors

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Chinese Medical Journal 2018年第11期131卷 1365-1366页

作者： Hui-Nian Zhou Yan-Xian Ren Long Li Ke-Shen Wang Zuo-Yi Jiao Department of General Surgery Lanzhou University Second Hospital Lanzhou University Lanzhou Gansu 730030 China

To the Editor： rho GTPase Activating Protein 1 IA （ArhGAPllA） is a member of the rho GTPase-activating proteins （rho GAPs） gene family and is located on the long arm of 15 chromosome region 1 band 3 subband 2 （ 15q 13.3）. The full-length cDNA of ArhGAPIIA is 24,806 bp with a single open-reading frame. ArhGAPIIA is encoded by 13 exons and the encoded protein has three domains： a rhoGAP domain near the N terminus （amino acids 46-246）, and two uncharacterized domains respectively located in the center （387 516） and C terminus （590-997） of the protein.

关键词： GTPase 编码蛋白质 rho 激活肿瘤 cDNA 中心定位染色体

Subcellular localization of rho GTPases: implications for axon regeneration

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Neural Regeneration Research 2015年第7期10卷 1032-1033页

作者： Di Anna L.Hynds Department of Biology Texas Woman's University

Damage to neurons in the central nervous system often leads to a permanent loss of function due to several factors,including reduced capacity of axons to regenerate and an environment that inhibits axon regeneration because of disruption of myelin and the formation of a growth-refractory glial scar around the injury（Yoon and Tuszynski,2012）.

关键词： rho Subcellular localization of rho GTPases GTPase

Fasudil hydrochloride differentiates bone marrow mesenchymal stem cells into neurons via notch signaling

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Neural Regeneration Research 2010年第11期5卷 814-819页

作者： Eryi Zhao Liudong Wang Quanqing Wen Wenjuan Guan Jingjing Lu Tao Peng Boai Zhang Yanjie Jia Department of Neurology First Affiliated Hospital Zhengzhou University Zhengzhou 450052 Henan Province China

BACKGROUND： Notch signaling regulates bone marrow mesenchymal stem cell （MSC） proliferation, differentiation, and apoptosis, Notch signaling and rho kinase signaling exhibit a crosstalk phenomenon with JAK/STAT, and both participate in the neuronal dendritic spine development. Inhibition of rhoA/rho kinase signaling may regulate MSC differentiation into neuronal-like cells. OBJECTIVE： To investigate the effect of Notch1 signaling on the differentiation of rat MSCs into neurons induced by fasudil hydrochloride （C14H17N3O2S-HCI）, a rho kinase inhibitor, through a siRNA approach. DESIGN, TIME AND SETTING： An in vitro cytological experiment was performed in the Cell Laboratory of Henan Academy of Medical and Pharmaceutical Sciences between December 2007 and May 2009. MATERIALS： MSCs were obtained from Wistar rat femoral bone, fasudil hydrochloride was provided by -Tianjin Chase Sun Pharmaceutical Co., Ltd. Rn-notchl-siRNa, negative control siRNA （Cy3 label） and Rn-MAPK1 control siRNA were provided by QIAGEN, Coloqne, German. METHODS： The cultured MSCs were divided into non-transfected, transfected group （transfected with Rn-Notchl-siRNA）, positive control （transfected with Rn-MAPK-1 control siRNA）, and negative control （transfected with negative control siRNA） groups. Fasudil hydrochloride was applied to induce MSCs to differentiate into neurons. MAIN OUTCOME MEASURES： The fluorescence expression by the transfected MSCs was observed under an inverted fluorescence microscope; the expression of Notch1 mRNA, Hesl mRNA, and MAPK1 mRNA in MSCs was detected by reverse transcription polymerase chain reaction; the expression of Notch1 protein, nestin, neurofilament M, and glial fibrillary acidic protein was detected by immunocytochemistry. The viability of MSCs was detected by tetrazolium bromide assay. RESULTS： MSC fluorescence increased following a 72-hour siRNA transfection, with transfection efficiencies of up to （0.91 ± 0.04）; the Notch1 mRNA and Hesl mRNA expressed by transfected MSCs was significantly decreased （P 〈 0

关键词： Notch rho fasudil hydrochloride marrow mesenchymal stem cells neuronal-like cells transfection nerve stem cells neural regeneration