Skip to main content
Springer Nature Link
Log in

Amyloid β cytotoxicity is enhanced or reduced depending on formation of amyloid β oligomeric forms

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Objectives

We explored the underlying mechanisms that facilitate reducing and enhancing effects of exogenous proteins on cytotoxicity of amyloid β (Aβ), a main pathogen of Alzheimer’s disease, by using an Escherichia coli chaperonin DnaK.

Results

DnaK was chosen as a tool, because it, easily available and functionally stable, reduced or enhanced Aβ cytotoxicity depending on its concentration. Cytotoxicity was enhanced when the molar ratio of DnaK to Aβ42, at 20 μM Aβ42, was 0.01–0.5, while reduced cytotoxicity was observed at higher ratios (> 1) at 1 μM Aβ42. Significant amounts of oligomeric Aβ42 species accumulated concomitantly with enhanced cytotoxicity, whereas the oligomers appeared to form complexes with DnaK in conditions of reduced cytotoxicity.

Conclusions

The difference in cytotoxicity was due to variations in the toxic oligomeric Aβ species and DnaK is a useful tool for the study of the Aβ ultrastructure formation and toxicity of Aβ peptide.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

Abbreviations

AD:

Alzheimer’s disease

Aβ:

Amyloid beta

ADDLs:

Aβ-derived diffusible ligands

CD:

Circular dichroism spectroscopy

MBP:

Maltose-binding protein

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide

RFU:

Relative fluorescence unit

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

TEM:

Transmission electron microscopy

ThT:

Thioflavin T

References

  • Adlard PA, Perreau VM, Pop V, Cotman CW (2005) Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. J Neurosci 25:4217–4221

    Article  CAS  Google Scholar 

  • Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, Glabe C (1992) Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J Biol Chem 267:546–554

    Article  CAS  Google Scholar 

  • Folin M, Baiguera S, Guidolin D, Di Liddo R, Grandi C, De Carlo E, Nussdorfer GG, Parnigotto PP (2006) Apolipoprotein-E modulates the cytotoxic effect of beta-amyloid on rat brain endothelium in an isoform-dependent specific manner. Int J Mol Med 17:821–826

    CAS  PubMed  Google Scholar 

  • Fonte V, Kapulkin V, Taft A, Fluet A, Friedman D, Link CD (2002) Interaction of intracellular beta amyloid peptide with chaperone proteins. Proc Natl Acad Sci USA 99:9439–9444

    Article  CAS  Google Scholar 

  • Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119:203–210

    Article  CAS  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  CAS  Google Scholar 

  • Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381:571–579

    Article  CAS  Google Scholar 

  • Islam MI, Sharoar MG, Ryu EK, Park IS (2017) Limited activation of the intrinsic apoptotic pathway plays a main role in amyloid-beta-induced apoptosis without eliciting the activation of the extrinsic apoptotic pathway. Int J Mol Med 40:1971–1982

    CAS  PubMed  Google Scholar 

  • Klein WL (2002) Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets. Neurochem Int 41:345–352

    Article  CAS  Google Scholar 

  • Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL et al (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95:6448–6453

    Article  CAS  Google Scholar 

  • Mattson MP (2004) Pathways towards and away from Alzheimer's disease. Nature 430:631–639

    Article  CAS  Google Scholar 

  • Nelson TJ, Alkon DL (2007) Protection against beta-amyloid induced apoptosis by peptides interacting with beta-amyloid. J Biol Chem 282:31238–31249

    Article  CAS  Google Scholar 

  • Shahnawaz M, Sharoar MG, Shin SY, Park IS (2013) Wild-type, Flemish, and Dutch amyloid-beta exhibit different cytotoxicities depending on Abeta40 to Abeta42 interaction time and concentration ratio. J Pept Sci 19:545–553

    Article  CAS  Google Scholar 

  • Sharoar MG, Shahnawaz M, Islam MI, Ramasamy VS, Shin SY, Park IS (2013) The inhibitory effects of Escherichia coli maltose binding protein on beta-amyloid aggregation and cytotoxicity. Arch Biochem Biophys 538:41–48

    Article  CAS  Google Scholar 

  • Zou K, Gong JS, Yanagisawa K, Michikawa M (2002) A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage. J Neurosci 22:4833–4841

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by research fund from Chosun University 2014 to I.S.P.

Author information

Author notes

  1. Md. Shahnawaz

    Present address: Department of Neurology, Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, The University of Texas Health Science Center at Houston, 6431 Fannin St, Houston, TX, 77030, USA

  2. Md. Shahnawaz and Tahmina Bilkis contributed equally.

Authors and Affiliations

  1. Department of Medical Science, College of Medicine, Chosun University, Gwangju, 501-759, Republic of Korea

    Md. Shahnawaz, Tahmina Bilkis & Il-Seon Park

  2. Department of Cell and Molecular Medicine, College of Medicine, Chosun University, Gwangju, 501-759, Republic of Korea

    Il-Seon Park

Authors
  1. Md. Shahnawaz
    View author publications

    Search author on:PubMed Google Scholar

  2. Tahmina Bilkis
    View author publications

    Search author on:PubMed Google Scholar

  3. Il-Seon Park
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Il-Seon Park.

Ethics declarations

Conflict of interest

All authors declares that they have no conflicts of interest to this work.

Research involving human and animal participants

This article does not contain any studies with human participants performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shahnawaz, M., Bilkis, T. & Park, IS. Amyloid β cytotoxicity is enhanced or reduced depending on formation of amyloid β oligomeric forms. Biotechnol Lett 43, 165–175 (2021). https://doi.org/10.1007/s10529-020-03015-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-020-03015-8

Keywords