Open Access Open Access  Restricted Access Subscription Access

Transcriptomic Response of Caenorhabditis elegans Expressing Human Aβ42 Gene Treated with Salvianolic Acid A


Affiliations
1 School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
2 USM-RIKEN International Centre for Ageing Science, Universiti Sains Malaysia, 11800 Penang, Malaysia
 

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
Notifications
Font Size

  • 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: 291

PDF Views: 133




  • Transcriptomic Response of Caenorhabditis elegans Expressing Human Aβ42 Gene Treated with Salvianolic Acid A

Abstract Views: 291  |  PDF Views: 133

Authors

Chee Wah Yuen
School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
Mardani Abdul Halim
USM-RIKEN International Centre for Ageing Science, Universiti Sains Malaysia, 11800 Penang, Malaysia
Nazalan Najimudin
School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
Ghows Azzam
School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia

Abstract


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.

References





DOI: https://doi.org/10.18520/cs%2Fv120%2Fi12%2F1882-1893