Purified high molecular weight synthetic Aβ(1-42) and biological Aβ oligomers are equipotent in rapidly inducing MTT formazan exocytosis

Adam M. Weidner, Molly Housley, M. Paul Murphy, Harry LeVine

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Synthetic soluble Aβ oligomers are often used as a surrogate for biologic material in a number of model systems. We compared the activity of Aβ oligomers (synthetic and cell culture media derived) on the human SH-SY5Y neuroblastoma and C2C12 mouse myoblast cell lines in a novel, modified MTT assay. Separating oligomers from monomeric peptide by size exclusion chromatography produced effects at peptide concentrations approaching physiologic levels (10-100nM). Purified oligomers, but not monomers or fibrils, elicited an increase of a detergent-insoluble form of MTT formazan within 2h as opposed to a control toxin (H2O2). This effect was comparable for biological and synthetic peptide in both cell types. Monomeric Aβ attenuated the effect of soluble oligomers. This study suggests that the activities of biological and synthetic oligomers are indistinguishable during early stages of Aβ oligomer-cell interaction.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalNeuroscience Letters
Volume497
Issue number1
DOIs
StatePublished - Jun 15 2011

Bibliographical note

Funding Information:
The authors would like to acknowledge the contribution of Dr. Susan Catalano of Cognition Therapeutics (Pittsburgh, PA) for studies with primary rat neuronal cultures. We also acknowledge the support of NIH/NIA grants NS058382 (M.P.M., A.M.W.), AG005119 (M.P.M., H.L.) and the Alzheimer's Association IIRG-06-27275 (A.M.W., H.L.). M.H. was supported by an NSF REU Site grant ( DBI-0648233 ).

Keywords

  • C2C12 myoblast
  • ELISA
  • H4 neuroglioma
  • SH-SY5Y neuroblastoma
  • Size exclusion chromatography

ASJC Scopus subject areas

  • General Neuroscience

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