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Emerging roles and therapeutic potentials of sphingolipids in pathophysiology:emphasis on fatty acyl heterogeneity

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Journal of Genetics and Genomics 2024年第3期51卷 268-278页

作者： Jinming Mu Sin Man Lam Guanghou Shui State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Lipidall Technologies Company Limited ChangzhouJiangsu 213000China

Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.

关键词： Sphingolipids Ceramide Therapeutic targets Microdomain Biomarker

ISOLATION, PURIFICATION & PROPERTIES OF LACTOSE BINDING AGGLUTINATION FACTOR FROM RABBIT SKELETAL MUSCLE

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Science in China,Ser.B 1984年第3期27卷 257-264页

作者：梁荣梯史赢仙 institute of developmental biology Academia Sinica Beijing

The lactose binding agglutination factor from rabbit skeletal muscle is isolated throughthe use of lactose and urea. The factor is purified with DEAE cellulose and Sepharose 4Bchromatography. The molecular weight of the factor is determined with Sephadex G-75chromatography and found to be 28,000 Daltens. The subunit’s molecular weight is deter-mined by SDS gel electrophoresis, and found to be 14,000 Daltens. It was found that thisbinding factor can agglutinate trypsin-treated rabbit erythrocytes. Moreover, this agglutina-tion is inhibited by EDTA and lactose.

关键词： PROPERTIES OF LACTOSE BINDING AGGLUTINATION FACTOR FROM RABBIT SKELETAL MUSCLE PURIFICATION ISOLATION

PURIFICATION AND CHARACTERIZATION OF A DNA POLYMERASE-TEMPLATE COMPLEX IN MOUSE ASCITES TUMOR CELLS

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Science in China,Ser.B 1982年第8期25卷 837-847页

作者：吴石君萧淑熙 institute of developmental biology Academia Sinica Beijing

A DNA polymerase-template complex found in mouse Erhlich ascites tumor cells waspurified by twice discontinuous gradient centrifugations and agarose gel filtration. Afterpurification, the specific activity of the complex increased about 500-fold. The size of thecomplex was found to be 510,000 daltons. The shape of the complex was globular under electronmieroscope. Its diameter was between 100--110 A. The complex was isolated into two mainenzyme proteins and a homogeneous DNA template by DEAE cellulose chromatography. Themain enzyme had a molecular weight of 300,000 daltons and a sedimentation coefficient of9.5s. The endogenous template DNA showed a single zone in polyacrylamide gel electropho-resis analysis. The sedimentation coefficient was determined to be 3.8s.

关键词： DNA PURIFICATION AND CHARACTERIZATION OF A DNA POLYMERASE-TEMPLATE COMPLEX IN MOUSE ASCITES TUMOR CELLS

JNK pathway:diseases and therapeutic potential

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Acta Pharmacologica Sinica 2007年第5期28卷 601-608页

作者： Jie CUI~(2,3),Ming ZHANG~(2,3),Yong-qing ZHANG~2,Zhi-heng XU~(2,4)~2Laboratory of Molecular and developmental biology,institute of Genetics and developmental biology and ~3Graduate School,ChineseAcademy of Sciences,Beijing 100101,China Laboratory of Molecular and developmental biology Institute of Genetics and Developmental Biology Beijing China Graduate School Chinese Academy of Sciences Beijing China

c-Jun N-terminal protein kinases (JNK),also known as stress-activated proteinkinases,were originally identified by their ability to phosphorylate the N-terminalof the transcription factor c-Jun and by their activation in response to a variety ofstresses.JNK are multifunctional kinases involved in many physiologicalprocesses.The JNK pathway has been shown to play a major role in apoptosis inmany cell death paradigms and its association with a variety of pathological pro-cesses is gradually been recognized.This review will concentrate on describingthe involvement of the JNK pathway in the context of different diseases and thepotential to adopt the JNK pathway components as therapeutic targets.

关键词： JNK pathway signal transduction diseases inhibitors

Non-B-form DNA is associated with centromere stability in newly-formed polyploid wheat

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Science China(Life Sciences) 2024年第7期67卷 1479-1488页

作者： Congyang Yi Qian Liu Yuhong Huang Chang Liu Xianrui Guo Chaolan Fan Kaibiao Zhang Yang Liu Fangpu Han institute of Genetics and developmental biology Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and transcription.However,the role of non-B-form DNA in centromeres,especially in polyploid wheat,remains elusive.Here,we systematically analyzed seven non-B-form DNA motif profiles(A-phased DNA repeat,direct repeat,G-quadruplex,inverted repeat,mirror repeat,short tandem repeat,and Z-DNA)in hexaploid wheat.We found that three of these non-B-form DNA motifs were enriched at centromeric regions,especially at the CENH3-binding sites,suggesting that non-B-form DNA may create a favorable loading environment for the CENH3 nucleosome.To investigate the dynamics of centromeric non-B form DNA during the alloploidization process,we analyzed DNA secondary structure using CENH3 ChIP-seq data from newly formed allotetraploid wheat and its two diploid ancestors.We found that newly formed allotetraploid wheat formed more non-B-form DNA in centromeric regions compared with their parents,suggesting that non-B-form DNA is related to the localization of the centromeric regions in newly formed wheat.Furthermore,non-B-form DNA enriched in the centromeric regions was found to preferentially form on young LTR retrotransposons,explaining CENH3's tendency to bind to younger LTR.Collectively,our study describes the landscape of non-B-form DNA in the wheat genome,and sheds light on its potential role in the evolution of polyploid centromeres.

关键词： non-B-form DNA polyploid wheat centromere retrotransposon

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GreenPhos,a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility

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Molecular Plant 2024年第1期17卷 199-213页

作者： Xiaoxiao Duan Yuanya Zhang Xiahe Huang Xiao Ma Hui Gao Yan Wang Zhen Xiao Chengcheng Huang Zhongshu Wang Bolong Li Wenqiang Yang Yingchun Wang State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBejing 100101China University of Chinese Academy of Sciences Bejing 100049China Key Laboratory of Photobiology Instute of BotanyChinese Academy of SciencesBejing 100093China

Protein phosphorylation regulates a variety of important cellular and physiological processes in plants.In-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal phosphoproteomes.This is largely due to the need to improve protein extraction efficiency from plant cells,which have a dense cell wall,and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry analysis.To this end,we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis,rice,tomato,and Chlamydomonas reinhardtii,enabling in-depth identification with high quantitative reproducibility of about 11000 phosphosites,the greatest depth achieved so far with single liquid chromatography-mass spectrometry(LC-MS)runs operated in a data-dependent acquisition(DDA)mode.The mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time-and cost-effectiveness.The method,named GreenPhos,combined with single-shot LC-MS,enabled in-depth quantitative identification of Arabidopsis phosphoproteins,including differentially phosphorylated spliceosomal proteins,at multiple time points during salt stress and a number of kinase substrate motifs.GreenPhos is expected to serve as a universal method for purification of plant phosphopeptides,which,if samples are further fractionated and analyzed by multiple LC-MS runs,could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

关键词： plant phosphoproteomics phosphopeptides LC–MS Arabidopsis salt stress

Rice GTPase OsRacB:Potential Accessory Factor in Plant Salt-stress Signaling

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Acta Biochimica et Biophysica Sinica 2006年第6期38卷 393-402页

作者： Min LUO~(1,2),Su-Hai GU~1,Shu-Hui ZHAO~1,Fang ZHANG~1,and Nai-Hu WU~(1*) ~1 institute of Genetics and developmental biology,Chinese Academy of Sciences,Beijing 100080.China ~2 Deportment of Cell and developmental biology,Weill Medical College of Cornell University,New York.NY 10021.USA institute of Genetics and developmental biology Chinese Academy of SciencesBeijing 100080 China Department of Cell and developmental biology Weill Medical College of Cornell UniversityNew York NY 10021 USA

As the sole ubiquitous signal small guanosine triphosphate-binding protein in plants,Rop geneplays an important role in plant growth and development.In this study,we focus on the relationship betweenthe novel rice Rop gene OsRacB and plant salt tolerance.Results show that OsRacB transcription is highlyaccumulated in roots after treatment with salinity,but only slightly accumulated in stems and leaves under thesame treatment.Promoter analysis showed that OsRacB promoter is induced by salinity and exogenoussalicylic acid,not abscisic acid.To elucidate its physiological function,we generated OsRacB sense andantisense transgenic tobacco and rice.Under proper salinity treatment,sense transgenic plants grew muchbetter than the control.This suggests that overexpression of OsRacB in tobacco and rice can improve plantsalt tolerance.But under the same treatment,no difference could be observed between OsRacB antisenseplants and the control.The results indicated that OsRacB is only an accessory factor in plant salt tolerance.

关键词： OsRacB rice salt tolerance promoter transgenic analysis

Arabidopsis RAV1 is down-regulated by brassinosteroid and may act as a negative regulator during plant development

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Cell Research 2004年第1期14卷 8-15页

作者： Yu Xin HU~*, Yong Hong WANG~*, Xin Fang LIU, Jia Yang LI~(**) institute of Genetics and developmental biology, Chinese Academy of Sciences, Beijing 100101, China. institute of Genetics and developmental biology Chinese Academy of Sciences Beijing China

RAV1 is a novel DNA-binding protein with two distinct DNA-binding domains unique in higher plants, but its role in plant growth and development remains unknown. Using cDNA array, we found that transcription of RAV1 is downregulated by epibrassinolide (epiBL) in Arabidopsis suspension cells. RNA gel blot analysis revealed that epiBL-regulated RAV1 transcription involves neither protein phosphorylation/dephosphorylation nor newly synthesized protein, and does not require the functional BRI1, suggesting that this regulation might be through a new BR signaling pathway. Overexpressing RAV1 in Arabidopsis results in a retardation of lateral root and rosette leaf development, and the underexpression causes an earlier flowering phenotype, implying that RAV1 may function as a negative regulatory component of growth and development.

关键词： RAV1 Brassinosteroid signal transduction Arabidopsis thaliana.

D609 induces vascular endothelial cells and marrow stromal cells differentiation into neuron-like cells

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Acta Pharmacologica Sinica 2004年第4期25卷 44-48页

作者： Nan WANG, Chun-qing DU, Shao-shan WANG, Kun XIE, Shang-li ZHANG, Jun-ying MIAO2 institute of developmental biology, School of Life Science, Shandong University, Ji-nan 250100, China institute of developmental biology School of Life Science Shandong University Jinan 250100

AIM: To investigate the effect of tricyclodecane-9-yl-xanthogenate (D609) on cell differentiation in vascular endo- thelial cells (VECs) and marrow stromal cells (MSCs). METHODS: Morphological changes were observed under phase contrast microscope. Electron microscope and immunostaining were used for VECs identification. The expressions of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. RESULTS: After 6 h of induction with D609, some VECs showed morphological changes characteristic of neurones. 9 h later, more VECs became neuron-like cells. About 30.8 % of VECs displayed positive NSE (P<0.01), while the expression of GFAP was negative. When MSCs were exposed to D609, the cells displayed neuronal morphologies, such as pyramidal cell bodies and processes formed extensive networks at 3 h. 6 h later, almost all of the cells exhibited a typical neuronal appearance, and 85.6 % of MSCs displayed intensive positive NSE, but GFAP did not express. CONCLUSION: D609 induces VECs and MSCs differentiation into neuron-like cells.

关键词： tricyclodecane-9-yl-xanthogenate cell differentiation vascular endothelial cells marrow stromal cells neuron-like cells