Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jun;31(6):1055-8.
doi: 10.1016/j.neurobiolaging.2008.07.013. Epub 2008 Aug 30.

Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers

Yanjue Wu  1 , Zhiming Cao, William L Klein, Yuan Luo
Affiliations

Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers

Yanjue Wu et al. Neurobiol Aging. 2010 Jun.

Abstract

Heat shock response, mediated by heat shock proteins, is a highly conserved physiological process in multicellular organisms for reestablishment of cellular homeostasis. Expression of heat shock factors and subsequent heat shock protein plays a role in protection against proteotoxicity in invertebrate and vertebrate models. Proteotoxicity due to beta-amyloid peptide (Abeta) oligomerization has been linked to the pathogenesis of Alzheimer's disease. Previously, we demonstrated that progressive paralysis induced by expression of human Abeta(1-42) in transgenic Caenorhabditis elegans was alleviated by Abeta oligomer inhibitors Ginkgo biloba extract and its constituents [Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M.P., Klein, W.L., Link, C.D., Luo, Y., 2006. Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci. 26(50): 13102-13113]. In this study, we apply a protective heat shock to the transgenic C. elegans and demonstrate: (1) a delay in paralysis, (2) increased expression of small heat shock protein HSP16.2, and (3) significant reduction of Abeta oligomers in a heat shock time-dependent manner. These results suggest that transient heat shock lessens Abeta toxicity by diminishing Abeta oligomerization, which provides a link between up regulation of endogenous chaperone proteins and protection against Abeta proteotoxicity in vivo.

PubMed Disclaimer

Conflict of interest statement

Disclosure Statement Wu, Y., Cao, Z., Klein, WL and Luo, Y. do not have any actual or potential conflicts of interest with other people or organizations.

Figures

Figure 1
Figure 1
Aβ-induced paralysis (A) and levels of intracellular H2O2 (B) in transgenic C. elegans strain (Aβ worms) or wild type (Ctrl strain) with (+HS) or without (-HS) heat shock for 2h at 35°C. Each group contains 100 worms. Results were from three independent tests. *P<0.05, **P<0.01.
Figure 2
Figure 2
Western blots of small heat shock protein HSP16.2 (A), Aβ oligomers (antibody NU4) (B) or total Aβ (antibody 6E10) (C) in Aβ worms treated with increasing time of heat shock (0-5h). D. Mean density of Aβ oligomers (NU4) in wild type (Ctrl worms) or Aβ worms, untreated (-HS) or heat shocked (HS) for 2h. Data were obtained from three independent experiments (**P<0.01).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Boyd-Kimball D, Poon HF, Lynn BC, Cai J, Pierce WM, Jr, Klein JB, Ferguson J, Link CD, Butterfield DA. Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Abeta(1-42): implications for Alzheimer's disease. Neurobiol Aging. 2006;27(9):1239–49. - PubMed
    1. Bieschke J, Perciavalle RM, Kelly JW, Dillin A. Opposing activities protect against age-onset proteotoxicity. Science. 2006;313(5793):1604–10. - PubMed
    1. Fonte V, Kapulkin V, Taft A, Fluet A, Friedman D, Link CD. Interaction of intracellular beta amyloid peptide with chaperone proteins. Proc Natl Acad Sci USA. 2002;99:9439–44. - PMC - PubMed
    1. Fonte V, Kipp DR, Yerg J, 3rd, Merin D, Forrestal M, Wagner E, Roberts CM, Link CD. Suppression of in vivo beta amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J Biol Chem 2007 - PubMed
    1. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297(5580):353–6. - PubMed

Publication types

MeSH terms

  NODES
twitter 2