Dissociation of ERK signalling inhibition from the anti-amyloidogenic action of synthetic ceramide analogues

Additional Titles: Inhibition of GSL (glycosphingolipid) synthesis reduces Aβ (amyloid β-peptide) production in vitro. Previous studies indicate that GCS (glucosylceramide synthase) inhibitors modulate phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) and that the ERK pathway may regulate some aspects of Aβ production. It is not clear whether there is a causative relationship linking GSL synthesis inhibition, ERK phosphorylation and Aβ production. In the present study, we treated CHO cells (Chinese-hamster ovary cells) and SH-SY5Y neuroblastoma cells, that both constitutively express human wild-type APP (amyloid precursor protein) and process this to produce Aβ, with GSL-modulating agents to explore this relationship. We found that three related ceramide analogue GSL inhibitors, based on the PDMP (D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) structure, reduced cellular Aβ production and in all cases this was correlated with inhibition of pERK (phosphorylated ERK) formation. Importantly, the L-threo enantiomers of these compounds (that are inferior GSL synthesis inhibitors compared with the D-threo-enantiomers) also reduced ERK phosphorylation to a similar extent without altering Aβ production. Inhibition of ERK activation using either PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one] or U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) had no impact on Aβ production, and knockdown of endogenous GCS using small interfering RNA reduced cellular GSL levels without suppressing Aβ production or pERK formation. Our data suggest that the alteration in pERK levels following treatment with these ceramide analogues is not the principal mechanism involved in the inhibition of Aβ generation and that the ERK signalling pathway does not play a crucial role in processing APP through the amyloidogenic pathway.

Συγγραφείς: Li, H, Evin, G, Hill, AF, Hung, YH, Bush, AI, Garner, B

Όροι ευρετηρίου: Journal Article

Σύνδεσμος: https://hdl.handle.net/11343/112602

Dissociation of ERK signalling inhibition from the anti-amyloidogenic action of synthetic ceramide analogues

Additional Titles: Inhibition of GSL (glycosphingolipid) synthesis reduces Aβ (amyloid β-peptide) production in vitro. Previous studies indicate that GCS (glucosylceramide synthase) inhibitors modulate phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) and that the ERK pathway may regulate some aspects of Aβ production. It is not clear whether there is a causative relationship linking GSL synthesis inhibition, ERK phosphorylation and Aβ production. In the present study, we treated CHO cells (Chinese-hamster ovary cells) and SH-SY5Y neuroblastoma cells, that both constitutively express human wild-type APP (amyloid precursor protein) and process this to produce Aβ, with GSL-modulating agents to explore this relationship. We found that three related ceramide analogue GSL inhibitors, based on the PDMP (D-threo-1-phenyl-2-decanoylamino- 3-morpholino-1-propanol) structure, reduced cellular Aβ production and in all cases this was correlated with inhibition of pERK (phosphorylated ERK) formation. Importantly, the L-threo enantiomers of these compounds (that are inferior GSL synthesis inhibitors compared with the D-threo-enantiomers) also reduced ERK phosphorylation to a similar extent without altering Aβ production. Inhibition of ERK activation using either PD98059 [2-(2-amino-3-methoxyphenyl)-4H- 1-benzopyran-4-one] or U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) had no impact on Aβ production, and knockdown of endogenous GCS using small interfering RNA reduced cellular GSL levels without suppressing Aβ production or pERK formation. Our data suggest that the alteration in pERK levels following treatment with these ceramide analogues is not the principal mechanism involved in the inhibition of Aβ generation and that the ERK signalling pathway does not play a crucial role in processing APP through the amyloidogenic pathway.

Συγγραφείς: Li, Hongyun, Evin, Genevieve, Hill, Andrew F, HUNG, Ya Hui, BUSH, Ashley I, Garner, Brett

Πηγή: Faculty of Science - Papers (Archive)

Όροι ευρετηρίου: dissociation, erk, analogues, signalling, ceramide, inhibition, synthetic, action, amyloidogenic, anti, CMMB, Life Sciences, Physical Sciences and Mathematics, Social and Behavioral Sciences, article

Σύνδεσμος: https://ro.uow.edu.au/scipapers/4737
https://ro.uow.edu.au/context/scipapers/article/8080/viewcontent/downloadAttachmentForRo.pdf

Development of Small Interfering RNA-Loaded Extracellular Vesicles via a High-Pressure Homogenization Approach

Συγγραφείς: Fukuta, Tatsuya^aff1, Miyazaki, Masato^aff1, Fujimoto, Taiki^aff2, Shibaguchi, Kota^aff1, Matsui, Ko^aff3, Ikeda-Imafuku, Mayumi^aff1, Higashi, Kenjirou^aff2, Kadota, Kazunori^aff1

Πηγή: ACS Applied Bio Materials. 9(15):7038-7052

Διαθεσιμότητα: https://pubs.acs.org/doi/10.1021/acsabm.6c00676

Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia

Συγγραφείς: Flygare, Johan, Author, Kiefer, Thomas, Author, Miyake, Koichi, Author, Utsugisawa, Taiju, Author, Hamaguchi, Isao, Author, Da Costa, Lydie, Author, Richter, Johan, Author, Davey, Edward J, Author, Matsson, Hans, Author, Dahl, Niklas, Author, Wiznerowicz, Maciej, Author, Trono, Didier, Author, Karlsson, Stefan, Author

Συνεισφορές: Flygare, Johan, Author, Kiefer, Thomas, Author, Miyake, Koichi, Author, Utsugisawa, Taiju, Author, Hamaguchi, Isao, Author, Da Costa, Lydie, Author, Richter, Johan, Author, Davey, Edward J, Author, Matsson, Hans, Author, Dahl, Niklas, Author, Wiznerowicz, Maciej, Author, Trono, Didier, Author, Karlsson, Stefan, Author

Πηγή: Blood. 105(12):4627-4634

Θεματικοί όροι: Anemia, Diamond-Blackfan/*blood/pathology, Antigens, CD/biosynthesis, CD34/*biosynthesis, Differentiation, B-Lymphocyte/biosynthesis, Base Sequence, Blotting, Northern, Western, Bone Marrow Cells/cytology, Cell Differentiation, Cell Line, Cell Proliferation, Cell Separation, Cloning, Molecular, Down-Regulation, Erythroid Progenitor Cells/metabolism, Flow Cytometry, Gene Silencing, Genetic Vectors, Green Fluorescent Proteins/chemistry/metabolism, Hematopoiesis, Humans, Image Processing, Computer-Assisted, Lentivirus/genetics, Molecular Sequence Data, Phenotype, RNA, Messenger/metabolism, Small Interfering/*metabolism, Receptors, Transferrin, Reverse Transcriptase Polymerase Chain Reaction, Ribosomal Proteins/*deficiency/*physiology, Ribosomes/metabolism, Time Factors, Transgenes, Umbilical Cord/cytology, MEDICINE, MEDICIN

Περιγραφή αρχείου: print

Σύνδεσμος πρόσβασης: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-14989
https://doi.org/10.1182/blood-2004-08-3115

Small Interfering RNA (siRNA) in Dyslipidemia: A Systematic Review on Safety and Efficacy of siRNA.

Συγγραφείς: Alla, Sai Santhosha Mrudula, Shah, Dhruv Jayeshkumar, Meyur, Shourya, Agarwal, Pahel, Alla, Deekshitha, Moraboina, Sai Lokesh, Ghadvaje, Gayatri Vijay, Bayeh, Ruth Getaneh, Malireddi, Aparna, Shajan, Tess, Vineetha, Bodipudi, Prudhvi, Thalvayapati Sai, Biziyaremye, Patrick

Πηγή: Journal of Experimental Pharmacology; May2025, Vol. 17, p249-267, 19p

Θεματικοί όροι: RNA interference, Small interfering RNA, Internet servers, Diabetes, Apolipoproteins

Dynamically expressed small RNAs, substantially driven by genomic structural variants, contribute to transcriptomic changes during tomato domestication.

Συγγραφείς: Qing Y; Beijing Key Laboratory for Agricultural Application and New Technique, College of Plant Science and Technology, Beijing University of Agriculture, Beijing, 102206, China.; Bioinformatics Center, Beijing University of Agriculture, Beijing, 102206, China., Zheng Y; Beijing Key Laboratory for Agricultural Application and New Technique, College of Plant Science and Technology, Beijing University of Agriculture, Beijing, 102206, China.; Bioinformatics Center, Beijing University of Agriculture, Beijing, 102206, China.; Boyce Thompson Institute, Cornell University, Ithaca, NY, 14853, USA., Mlotshwa S; Department of Molecular Genetics, Ohio State University, Columbus, OH, 43210, USA., Smith HN; Department of Biological Sciences, Mississippi State University, Starkville, MS, 39759, USA., Wang X; Boyce Thompson Institute, Cornell University, Ithaca, NY, 14853, USA., Zhai X; Beijing Key Laboratory for Agricultural Application and New Technique, College of Plant Science and Technology, Beijing University of Agriculture, Beijing, 102206, China.; Bioinformatics Center, Beijing University of Agriculture, Beijing, 102206, China., van der Knaap E; Center for Applied Genetic Technologies, University of Georgia, Athens, GA, 30602, USA.; Institute for Plant Breeding, Genetics and Genomics, University of Georgia, Athens, GA, 30602, USA.; Department of Horticulture, University of Georgia, Athens, GA, 30602, USA., Wang Y; Department of Molecular Genetics, Ohio State University, Columbus, OH, 43210, USA.; Department of Biological Sciences, Mississippi State University, Starkville, MS, 39759, USA., Fei Z; Boyce Thompson Institute, Cornell University, Ithaca, NY, 14853, USA.; USDA-ARS, Robert W. Holley Center for Agriculture and Health, Ithaca, NY, 14853, USA.

Πηγή: The Plant journal : for cell and molecular biology [Plant J] 2022 Jun; Vol. 110 (6), pp. 1536-1550. Date of Electronic Publication: 2022 May 24.

Τύπος έκδοσης: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.

Στοιχεία περιοδικού: Publisher: Blackwell Scientific Publishers and BIOS Scientific Publishers in association with the Society for Experimental Biology Country of Publication: England NLM ID: 9207397 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-313X (Electronic) Linking ISSN: 09607412 NLM ISO Abbreviation: Plant J Subsets: MEDLINE

Ιατρικοί όροι (MeSH): Solanum lycopersicum*/genetics , Solanum lycopersicum*/metabolism , MicroRNAs*/genetics , MicroRNAs*/metabolism, Gene Expression Regulation, Plant/genetics ; RNA, Plant/genetics ; RNA, Small Interfering/genetics ; Transcriptome/genetics ; Domestication ; Genomic Structural Variation ; Nucleotides

Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay

Συγγραφείς: Hausburg, Melissa A, Doles, Jason D, Clement, Sandra L, Cadwallader, Adam B, Hall, Monica N, Blackshear, Perry J, Lykke-Andersen, Jens, Olwin, Bradley B

Πηγή: eLife. 4(4)

Θεματικοί όροι: 3208 Medical Physiology (for-2020), 32 Biomedical and Clinical Sciences (for-2020), Stem Cell Research (rcdc), Stem Cell Research - Nonembryonic - Non-Human (rcdc), Genetics (rcdc), 1.1 Normal biological development and functioning (hrcs-rac), Musculoskeletal (hrcs-hc), 3' Untranslated Regions (mesh), Animals (mesh), Base Sequence (mesh), Binding Sites (mesh), Cell Differentiation (mesh), Cell Proliferation (mesh), Female (mesh), Intracellular Signaling Peptides and Proteins (mesh), Male (mesh), Mice (mesh), Mice, Inbred C57BL (mesh), Mice, Transgenic (mesh), Molecular Sequence Data (mesh), Muscle, Skeletal (mesh), MyoD Protein (mesh), Protein Binding (mesh), Protein Serine-Threonine Kinases (mesh), RNA Processing, Post-Transcriptional (mesh), RNA Stability (mesh), RNA, Small Interfering (mesh), Regeneration (mesh), Satellite Cells, Skeletal Muscle (mesh), Signal Transduction (mesh), Tristetraprolin (mesh), p38 Mitogen-Activated Protein Kinases (mesh), Muscle, Skeletal (mesh), Satellite Cells, Skeletal Muscle (mesh), Animals (mesh), Mice, Inbred C57BL (mesh), Mice, Transgenic (mesh), Mice (mesh), p38 Mitogen-Activated Protein Kinases (mesh), Intracellular Signaling Peptides and Proteins (mesh), MyoD Protein (mesh), RNA, Small Interfering (mesh), 3' Untranslated Regions (mesh), Regeneration (mesh), Signal Transduction (mesh), Cell Differentiation (mesh), Cell Proliferation (mesh), RNA Processing, Post-Transcriptional (mesh), Binding Sites (mesh), Base Sequence (mesh), Protein Binding (mesh), RNA Stability (mesh), Molecular Sequence Data (mesh), Female (mesh), Male (mesh), Tristetraprolin (mesh), Protein Serine-Threonine Kinases (mesh), developmental biology, homeostasis, mouse, niche, quiescence, regeneration, skeletal muscle, stem cells, 3' Untranslated Regions (mesh), Animals (mesh), Base Sequence (mesh), Binding Sites (mesh), Cell Differentiation (mesh), Cell Proliferation (mesh), Female (mesh), Intracellular Signaling Peptides and Proteins (mesh), Male (mesh), Mice (mesh), Mice, Inbred C57BL (mesh), Mice, Transgenic (mesh), Molecular Sequence Data (mesh), Muscle, Skeletal (mesh), MyoD Protein (mesh), Protein Binding (mesh), Protein Serine-Threonine Kinases (mesh), RNA Processing, Post-Transcriptional (mesh), RNA Stability (mesh), RNA, Small Interfering (mesh), Regeneration (mesh), Satellite Cells, Skeletal Muscle (mesh), Signal Transduction (mesh), Tristetraprolin (mesh), p38 Mitogen-Activated Protein Kinases (mesh), 0601 Biochemistry and Cell Biology (for), 31 Biological sciences (for-2020), 32 Biomedical and clinical sciences (for-2020), 42 Health sciences (for-2020)

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Σύνδεσμος πρόσβασης: https://escholarship.org/uc/item/3838j8ft
https://escholarship.org/content/qt3838j8ft/qt3838j8ft.pdf

Function and Evolution of a MicroRNA That Regulates a Ca²⁺-ATPase and Triggers the Formation of Phased Small Interfering RNAs in Tomato Reproductive Growth

Συγγραφείς: Wang, Ying, Itaya, Asuka, Zhong, Xuehua, Wu, Yang, Zhang, Jianfeng, van der Knaap, Esther, Olmstead, Richard, Qi, Yijun, Ding, Biao

Πηγή: The Plant Cell, 2011 Sep 01. 23(9), 3185-3203.

Σύνδεσμος πρόσβασης: https://www.jstor.org/stable/41434691

长链非编码 RNA 1010001N08Rik 和 GATA6 在 高氧暴露小鼠肺癌细胞中表达和意义. (Chinese)

Alternate Title: Expression and Significance of Long non-coding RNA 1010001N08Rik and GATA 6 in Hyperoxia-exposed LLC Cells. (English)

Συγγραφείς: 罗 好, 刘怡波, 颜崇兵, 翁博雯, 蔡 成

Πηγή: Progress in Modern Biomedicine; 2024, Vol. 24 Issue 15, p2805-2816, 12p

Θεματικοί όροι: Gene expression, RNA interference, Small interfering RNA, LincRNA, Wnt proteins

Rscreenorm: normalization of CRISPR and siRNA screen data for more reproducible hit selection.

Συγγραφείς: Bachas, Costa^1,2 c.bachas@vumc.nl, Hodzic, Jasmina³ j.hodzic@vumc.nl, van der Mijn, Johannes C.³ j.vandermijn@vumc.nl, Stoepker, Chantal⁴ c.stoepker@nki.nl, Verheul, Henk M. W.³ h.verheul@vumc.nl, Wolthuis, Rob M. F.⁵ r.wolthuis@vumc.nl, Felley-Bosco, Emanuela⁶ emanuela.felley-bosco@usz.ch, van Wieringen, Wessel N.^2,7 w.vanwieringen@vumc.nl, van Beusechem, Victor W.³ vw.vanbeusechem@vumc.nl, Brakenhoff, Ruud H.¹ rh.brakenhoff@vumc.nl, de Menezes, Renée X.² r.menezes@vumc.nl

Πηγή: BMC Bioinformatics. 8/20/2018, Vol. 19 Issue 1, p1-12. 12p. 1 Chart, 5 Graphs.

Θεματικοί όροι: *CRISPRs, *Small interfering RNA, *Electronic data processing, *Standardization, *Cell lines, *Reproducible research, *Data modeling, *Data analysis

Off-target possibility of efficient siRNA using String matching

Συγγραφείς: Prameela, S., Jereesh, A. S.

Πηγή: 2017 International Conference on Circuit ,Power and Computing Technologies (ICCPCT) Circuit ,Power and Computing Technologies (ICCPCT), 2017 International Conference on. :1-5 Apr, 2017

Relation: 2017 International Conference on Circuit ,Power and Computing Technologies (ICCPCT)

PhasiRNAnalyzer: an integrated analyser for plant phased siRNAs.

Συγγραφείς: Fei, Yuhan, Feng, Jiejie, Wang, Rui, Zhang, Baoyi, Zhang, Hongsheng, Huang, Ji

Πηγή: RNA Biology; Nov 2021, Vol. 18 Issue 11, p1622-1629, 8p

Θεματικοί όροι: Small interfering RNA, Host plants, Internet servers, Botanists, Complementary DNA, Plant genomes, Plant gene silencing

MicroRNAs and Small Interfering RNAs Can Inhibit mRNA Expression by Similar Mechanisms

Συγγραφείς: Zeng, Yan, Yi, Rui, Cullen, Bryan R.

Πηγή: Proceedings of the National Academy of Sciences of the United States of America, 2003 Aug . 100(17), 9779-9784.

Σύνδεσμος πρόσβασης: https://www.jstor.org/stable/3147612

Design Rules for the Nano‐Bio Interface of Nanodiamonds: Implications for siRNA Vectorization.

Συγγραφείς: Kindermann, Marek, Neburkova, Jitka, Neuhoferova, Eva, Majer, Jan, Stejfova, Miroslava, Benson, Veronika, Cigler, Petr

Πηγή: Advanced Functional Materials; 7/24/2024, Vol. 34 Issue 30, p1-15, 15p

Θεματικοί όροι: Small interfering RNA, Nanodiamonds, RNA, Colloidal stability, Protective coatings, Acrylamide

Modern LC-MS strategies for comprehensive metabolite identification of therapeutic oligonucleotides

Συγγραφείς: Kumar, Devendra ^{a, ⁎}, Dahibhate, Nilesh ^b, Trivedi, Neerja ^c

Πηγή: In Journal of Chromatography B 1 May 2026 1275

The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells

Συγγραφείς: Ramos, Alexander D, Andersen, Rebecca E, Liu, Siyuan John, Nowakowski, Tomasz Jan, Hong, Sung Jun, Gertz, Caitlyn C, Salinas, Ryan D, Zarabi, Hosniya, Kriegstein, Arnold R, Lim, Daniel A

Πηγή: Cell Stem Cell. 16(4)

Θεματικοί όροι: 3206 Medical Biotechnology (for-2020), 31 Biological Sciences (for-2020), 32 Biomedical and Clinical Sciences (for-2020), Stem Cell Research - Nonembryonic - Human (rcdc), Genetics (rcdc), Stem Cell Research (rcdc), Neurosciences (rcdc), Regenerative Medicine (rcdc), Pediatric (rcdc), Stem Cell Research - Nonembryonic - Non-Human (rcdc), 1.1 Normal biological development and functioning (hrcs-rac), Neurological (hrcs-hc), Generic health relevance (hrcs-hc), Alternative Splicing (mesh), Animals (mesh), Base Sequence (mesh), Brain (mesh), Cells, Cultured (mesh), Embryo, Mammalian (mesh), Embryonic Stem Cells (mesh), Heterogeneous-Nuclear Ribonucleoproteins (mesh), Humans (mesh), Mice (mesh), Mice, Inbred C57BL (mesh), Molecular Sequence Data (mesh), Neural Stem Cells (mesh), Neurogenesis (mesh), Neurons (mesh), Polypyrimidine Tract-Binding Protein (mesh), RNA, Long Noncoding (mesh), RNA, Small Interfering (mesh), Brain (mesh), Neurons (mesh), Cells, Cultured (mesh), Animals (mesh), Mice, Inbred C57BL (mesh), Humans (mesh), Mice (mesh), Polypyrimidine Tract-Binding Protein (mesh), Heterogeneous-Nuclear Ribonucleoproteins (mesh), RNA, Small Interfering (mesh), Alternative Splicing (mesh), Base Sequence (mesh), Molecular Sequence Data (mesh), Embryonic Stem Cells (mesh), Embryo, Mammalian (mesh), Neurogenesis (mesh), Neural Stem Cells (mesh), RNA, Long Noncoding (mesh), Alternative Splicing (mesh), Animals (mesh), Base Sequence (mesh), Brain (mesh), Cells, Cultured (mesh), Embryo, Mammalian (mesh), Embryonic Stem Cells (mesh), Heterogeneous-Nuclear Ribonucleoproteins (mesh), Humans (mesh), Mice (mesh), Mice, Inbred C57BL (mesh), Molecular Sequence Data (mesh), Neural Stem Cells (mesh), Neurogenesis (mesh), Neurons (mesh), Polypyrimidine Tract-Binding Protein (mesh), RNA, Long Noncoding (mesh), RNA, Small Interfering (mesh), 06 Biological Sciences (for), 11 Medical and Health Sciences (for), Developmental Biology (science-metrix), 31 Biological sciences (for-2020), 32 Biomedical and clinical sciences (for-2020)

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https://escholarship.org/content/qt88t873rf/qt88t873rf.pdf

Rapid and flexible analytical characterization of oligonucleotides in early drug discovery

Συγγραφείς: Stavenhagen, Kathrin ^{a, ⁎}, Jora, Manasses ^a, Leandersson, Carina ^a, Rae, Rebecca ^a, Bourquin, Julien ^{b, 1}, Golghalyani, Vahid ^c, Czechtizky, Werngard ^a, Leek, Tomas ^a

Πηγή: In Journal of Chromatography A 4 January 2026 1765

Derivation and function of small interfering RNAs and microRNAs

Συγγραφείς: Cullen, Bryan R. ^∗

Πηγή: In Virus Research 2004 102(1):3-9

CRIT: Identifying RNA-binding protein regulator in circRNA life cycle via non-negative matrix factorization

Συγγραφείς: Shao, Mengting ^{1, 6}, Hao, Shijia ^{1, 6}, Jiang, Leiming ¹, Cai, Yujie ^{1, 2}, Zhao, Xing ^{1, 3}, Chen, Qiuyang ¹, Gao, Xuefei ^{4, 5}, Xu, Jianzhen ^{1, 5, ∗}

Πηγή: In Molecular Therapy - Nucleic Acids 13 December 2022 30:398-406

Stochastic model of siRNA endosomal escape mediated by fusogenic peptides

Συγγραφείς: Yadav, Nisha ^a, Boulos, Jessica ^b, Alexander-Bryant, Angela ^b, Cook, Keisha ^{a, ⁎}

Πηγή: In Mathematical Biosciences September 2025 387