Selective chemical intervention in the proteome of Caenorhabditis elegans

Holger Husi, Fiona McAllister, Nicos Angelopoulos, Victoria J. Butler, Kevin R. Bailey, Kirk Malone, Logan Mackay, Paul Taylor, Antony P. Page, Nicholas J. Turner, Perdita E. Barran, Malcolm Walkinshaw

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Abstract

We present the first study of protein regulation by ligands in Caenorhabditis elegans. The ligands were peptidyl-prolyl isomerase inhibitors of cyclophilins. Up-regulation is observed for several heat shock proteins and one ligand in particular caused a greater than 2-fold enhancement of cyclophilin CYN-5. Additionally, several metabolic enzymes display elevated levels. This approach, using label-free relative quantification, provides an extremely attractive way of measuring the effect of ligands on an entire proteome, with minimal sample pretreatment, which could be applicable to large-scale studies. In this initial study, which compares the effect of three ligands, 54 unique proteins have been identified that are up- (51) or down- (3) regulated in the presence of a given ligand. A total of 431 C. elegans proteins were identified. Our methodology provides an intriguing new direction for in vivo screening of the effects of novel and untested ligands at the whole organism level.
Original languageEnglish
Pages (from-to)6060-6070
Number of pages11
JournalJournal of Proteome Research
Volume9
Issue number11
DOIs
Publication statusPublished - 1 Nov 2010

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    Husi, H., McAllister, F., Angelopoulos, N., Butler, V. J., Bailey, K. R., Malone, K., Mackay, L., Taylor, P., Page, A. P., Turner, N. J., Barran, P. E., & Walkinshaw, M. (2010). Selective chemical intervention in the proteome of Caenorhabditis elegans. Journal of Proteome Research, 9(11), 6060-6070. https://doi.org/10.1021/pr100427c