Open Access
Subscription Access
Transcriptomic Response of Caenorhabditis elegans Expressing Human Aβ42 Gene Treated with Salvianolic Acid A
Alzheimer’s disease is associated with the deposition of β-amyloid peptide in the brain. A genome-wide transcriptomic study was performed to determine the response of transgenic Caenorhabditis elegans express-ing full-length human Aβ42 gene towards salvianolic acid A (Sal A). The genes associated with antioxidant response, gst-4, gst-10, spr-1 and trxr-2, were upregu-lated. Aβ42 caused oxidative stress and the antioxidant response genes possibly provide some sort of protec-tion to the nematode. trxr-2 gene product was also associated with the defence system and probably has a role in the lifespan of the nematode. Other genes involved in DNA replication, reproduction, immune res-ponse and antimicrobial activities were also found to be upregulated. Treatment of Sal A also increased the rate of reproduction in the nematode, and elevated its immunological protection system towards microor-ganisms. On the other hand, the genes responsible for ligand-gated cation channel, embryonic and postem-bryonic development, locomotion and neuromodula-tion of chemosensory neurons were found to be down-regulated. As an effector, Sal A might conceivably reduce the movement of the nematode by interfering with neuronal transmission, and embryonic and post-embryonic development.
Keywords
β-Amyloid Peptide, Caenorhabditis elegans, Salvianolic Acid A, Transcriptome.
User
Font Size
Information
- Ferri, C. P. et al., Global prevalence of dementia: a Delphi consensus study. Lancet, 2005, 366(9503), 2112–2117; doi:S0140-6736(05)67889-0 [pii]; 10.1016/S0140-6736(05)67889-0.
- Teplow, D. B., Yang, M., Roychaudhuri, R., Pang, E., Huynh, T. P., Chen, M. S. and Beroukhim, S., The amyloid beta-protein and Alzheimer’s disease. In Alzheimer’s Disease: Targets for New Clinical Diagnostic and Therapeutic Strategies (eds Wegryn, R. D. and Rudolph, A. S.), Taylor and Francis Group, Florida, USA, 2012, pp. 1–47.
- Hardy, J. A. and Higgins, G. A., Alzheimer’s disease: the amyloid cascade hypothesis. Science, 1992, 256(5054), 184–185.
- Kang, J. et al., The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature, 1987, 325(6106), 733–736; doi:10.1038/325733a0.
- Goate, A. et al., Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 1991, 349(6311), 704–706; doi:10.1038/349704a0.
- Glenner, G. G. and Wong, C. W., Alzheimer’s disease and down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem. Biophys. Res. Commun., 1984, 122(3), 1131–1135; doi:0006-291X(84)91209-9 [pii].
- Jia, Q., Deng, Y. and Qing, H., Potential therapeutic strategies for Alzheimer’s disease targeting or beyond beta-amyloid: insights from clinical trials. Biomed. Res. Int., 2014, 837157; doi: 10.1155/2014/837157.
- Xu, J. Z., Shen, J., Cheng, Y. Y. and Qu, H. B., Simultaneous detection of seven phenolic acids in Danshen injection using HPLC with ultraviolet detector. J. Zhejiang Univ. Sci. B, 2008, 9(9), 728–733.
- Lin, T. J., Zhang, K. J. and Liu, G. T., Effects of salvianolic acid A on oxygen radicals released by rat neutrophils and on neutrophil function. Biochem. Pharmacol., 1996, 51(9), 1237–1241.
- Zhang, H., Liu, Y. Y., Jiang, Q., Li, K. R., Zhao, Y. X., Cao, C. and Yao, J., Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling. Free Radic. Biol. Med., 2014, 69, 219–228.
- Yan, X., Dan Shen (Salvia miltiorrhiza). In Medicine Volume 2. Pharmacology and Quality Control, Springer, 2015.
- Yuen, C.-W., Halim, M. A., Najimudin, N. and Azzam, G., Effects of salvianolic acid A on -amyloid mediated toxicity in Caenor-habditis elegans model of Alzheimer’s disease. bioRxiv, 2020.
- He, F., Total RNA extraction from C. elegans. Bio-protocol., 2011, Bio101, e47 (e-book).
- Langmead, B., Trapnell, C., Pop, M. and Salzberg, S. L., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol., 2009, 10(3); doi:10.1186/gb-2009-10-3-r25.
- Langmead, B. and Salzberg, S. L., Fast gapped-read alignment with Bowtie 2. Nat. Methods, 2012, 9(4), 357–359; doi:10.1038/ nmeth.1923.
- Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R. and Salzberg, S. L., TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol., 2013, 14(4), R36; doi:10.1186/gb-2013-14-4-r36.
- Anders, S., Pyl, P. T. and Huber, W., HTSeq – a Python framework to work with high-throughput sequencing data. Bioinformatics, 2015, 31(2), 166–169; doi:10.1093/ bioinformatics/btu638.
- Trapnell, C. et al., Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnol., 2010, 28(5), 511–515; doi:10.1038/nbt.1621.
- Anders, S. and Huber, W., Differential expression analysis for sequence count data. Genome Biol., 2010, 11(10), R106; doi: 10.1186/gb-2010-11-10-r106.
- Robinson, M. D., McCarthy, D. J. and Smyth, G. K., edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 2010, 26(1), 139–140; doi:10.1093/bioinformatics/btp616.
- Wang, L., Feng, Z., Wang, X., Wang, X. and Zhang, X., DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics, 2010, 26(1), 136–138; doi:10.1093/bioinformatics/btp612.
- Benjamini, Y. and Hochberg, Y., Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B, 1995, 57(1), 289–300.
- Young, M. D., Wakefield, M. J., Smyth, G. K. and Oshlack, A., Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol., 2010, 11(2), R14; doi:10.1186/gb-2010-11-2-r14.
- Mao, X., Cai, T., Olyarchuk, J. G. and Wei, L., Automated genome annotation and pathway identification using the KEGG orthology (KO) as a controlled vocabulary. Bioinformatics, 2005, 21(19), 3787–3793; doi:10.1093/bioinformatics/bti430.
- Zhang, Y., Chen, D., Smith, M. A., Zhang, B. and Pan, X., Selection of reliable reference genes in Caenorhabditis elegans for analysis of nanotoxicity. PLoS ONE, 2012, 7(3), e31849; doi:10.1371/journal.pone.0031849.
- Prince, M., Ali, G., Guerchet, M., Prina, A., Albanese, E. and Wu, Y., Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res. Ther., 2016, 8(23), 1–13.
- Liu, C.-L., Xie, L.-X., Li, M., Durairajan, S. S. K., Goto, S. and Huang, J.-D., Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling. PLoS ONE, 2007, 2(12), e1321.
- Coles, M., Bicknell, W., Watson, A. A., Fairlie, D. P. and Craik, D. J., Solution structure of amyloid -peptide (1–40) in a water–micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry, 1998, 37(31), 11064–11077.
- Ayyadevara, S. et al., Lifespan and stress resistance of Caenorhabditis elegans are increased by expression of glutathione transferases capable of metabolizing the lipid peroxidation product 4-hydroxynonenal. Aging Cell, 2005, 4(5), 257–271; doi:10.1111/j.1474-9726.2005.00168.x.
- Leiers, B., Kampkotter, A., Grevelding, C. G., Link, C. D., Johnson, T. E. and Henkle-Duhrsen, K., A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radic. Biol. Med., 2003, 34(11), 1405–1415.
- Lu, T. et al., REST and stress resistance in ageing and Alzheimer’s disease. Nature, 2014, 507(7493), 448–454; doi: 10.1038/nature13163.
- Murphy, C. T. et al., Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature, 2003, 424(6946), 277–283; doi:10.1038/nature01789.
- Ayyadevara, S., Dandapat A., Singh, S. P., Benes, H., Zimniak, L., Shmookler Reis, R. J. and Zimniak, P., Lifespan extension in hypomorphic daf-2 mutants of Caenorhabditis elegans is partially mediated by glutathione transferase CeGSTP2-2. Aging Cell, 2005, 4(6), 299–307; doi:10.1111/j.1474-9726.2005.00172.x.
- Jarriault, S. and Greenwald, I., Suppressors of the egg-laying defective phenotype of sel-12 presenilin mutants implicate the CoREST corepressor complex in LIN-12/Notch signaling in C. elegans. Genes Develop., 2002, 16(20), 2713–2728.
- Doonan, R. et al., Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans, Genes Dev., 2008, 22(23), 3236–3241; doi:10.1101/gad.504808.
- Van Raamsdonk, J. M. and Hekimi, S., Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet, 2009, 5(2), e1000361; doi:10.1371/journal.pgen.1000361.
- Yang, W., Li, J. and Hekimi, S. A., Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics, 2007, 177(4), 2063–2074; doi:10.1534/genetics.107.080788.
- Yen, K., Patel, H. B., Lublin, A. L. and Mobbs, C. V., SOD isoforms play no role in lifespan in ad lib or dietary restricted conditions, but mutational inactivation of SOD-1 reduces life extension by cold. Mech. Ageing. Dev., 2009, 130(3), 173–178; doi:10.1016/j.mad.2008.11.003.
- Cabreiro, F. et al., Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic. Biol. Med., 2011, 51(8), 1575–1582; doi:10.1016/j.freeradbiomed.2011.07.020.
- Cacho-Valadez, B. et al., The characterization of the Caenorhabditis elegans mitochondrial thioredoxin system uncovers an unexpected protective role of thioredoxin reductase 2 in beta-amyloid peptide toxicity. Antioxid Redox Signal., 2012, 16(12), 1384–1400; doi:10.1089/ars.2011.4265.
- Goedert, M. et al., PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J. Cell Sci., 1996, 109(Pt 11), 2661–2672.
- McDermott, J. B., Aamodt, S. and Aamodt, E., ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins. Biochemistry, 1996, 35(29), 9415–9423; doi:10.1021/bi952646n.
- Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P., Molecular Biology of the Cell, Garland Science, New York, USA, 2002, 4th edn.
- Pujol, N., Zugasti, O., Wong, D., Couillault, C., Kurz, C. L., Schulenburg, H. and Ewbank, J. J., Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides. PLoS Pathog., 2008, 4(7), e1000105.
- Peden, A. S. et al., Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans. Nature Neurosci., 2013, 16(12), 1794–1801; doi:10.1038/nn.3575.
- Olsen, A. and Gill, M. S., Ageing: lessons from C. elegans. In Healthy Ageing and Longevity, Springer International, Switzer-land, 2017.
- Riddle, D. L., Blumenthal, T., Meyer, B. J. and Priess, J. R., C. elegans II, vol. 33, Cold Spring Harbor Laboratory Press, 1997, 2nd edn.
- Beales, P. L., Warner, A. M., Hitman, G. A., Thakker, R. and Flinter, F. A., Bardet–Biedl syndrome: a molecular and phenotypic study of 18 families. J. Med. Genet., 1997, 34(2), 92–98.
- Zinovyeva, A. Y. and Forrester, W. C., The C. elegans frizzled CFZ-2 is required for cell migration and interacts with multiple Wnt signaling pathways. Dev. Biol., 2005, 285(2), 447–461; doi:10.1016/j.ydbio.2005.07.014.
- Kennerdell, J. R., Fetter, R. D. and Bargmann, C. I., Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance
- and nerve ring placement in C. elegans. Development, 2009, 136(22), 3801–3810; doi:10.1242/dev.038109.
- Song, S. et al., Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis elegans. PLoS Genet., 2010, 6(8), doi:10.1371/journal.pgen.1001056.
- Hu, H., Li, Q., Jiang, L., Zou, Y., Duan, J. and Sun, Z., Genome-wide transcriptional analysis of silica nanoparticle-induced toxicity in zebrafish embryos. Toxicol Res., 2016, 5(2), 609–620.
- Marston, D. J., Roh, M., Mikels, A. J., Nusse, R. and Goldstein, B., Wnt signaling during Caenorhabditis elegans embryonic development. Meth. Mol. Biol., 2008, 469, 103–111; doi:10.1007/ 978-1-60327-469-9.
- Foehr, M. L. and Liu, J., Dorsoventral patterning of the C. elegans postembryonic mesoderm requires both LIN-12/Notch and TGFbeta signaling. Dev. Biol., 2008, 313(1), 256–266; doi: 10.1016/j.ydbio.2007.10.027.
Abstract Views: 276
PDF Views: 126