Characterisation of hookworm heat shock factor binding protein (HSB-1) during heat shock and larval activation

Document Type

Journal Article

Publication Date

4-1-2011

Journal

International Journal for Parasitology

Volume

41

Issue

5

DOI

10.1016/j.ijpara.2010.12.001

Keywords

Activation; Ancylostoma caninum; Heat shock factor; Heat shock response; Hookworms; Transition to parasitism

Abstract

When hookworm infective L3s infect their mammalian host, they undergo a temperature shift from that of the ambient environment to that of their endothermic host. Additionally, L3s living in the environment can be exposed to temperature extremes associated with weather fluctuations. The heat shock response (HSR) is a conserved response to heat shock and other stress that involves the expression of protective heat shock proteins (HSPs). The HSR is controlled by heat shock factor-1 (HSF-1), a conserved transcription factor that binds to a heat shock element in the promoter of HSPs, causing their expression. HSF-1 is negatively regulated in part by a HSF binding protein (HSB-1) that binds to and removes HSF-1 trimers bound to HSP gene promoters, resulting in attenuation of the HSR. Herein we describe an HSB-1 orthologue, Ac-HSB-1, from the hookworm Ancylostoma caninum. The Ac-hsb-1 cDNA encodes a 79 amino acid protein that is 71% identical to the Caenorhabditis elegans HSB-1, and is predicted to share the characteristic coiled-coil structural motif comprised of two interacting alpha helices. Recombinant Ac-HSB-1 immunoprecipitated Ce-HSF-1 expressed in mammalian cells that had been heat shocked for 1. h at 42. °C, but not from cells incubated at 37. °C, indicating that HSB-1 only bound to the active DNA binding form of HSF-1. Expression of Ac-hsb-1 transcripts decreased following 1. h of heat shock, but increased when L3s were incubated at 37. °C for 1. h. Activation of hookworm L3s induces a five-sixfold increase in Ac-hsb-1 expression that peaks at 12. h, coincident with L3 feeding, but that subsequently decreases to two-threefold above control at 24. h. Recombinant Ac-HSB-1 immunoprecipitates greater amounts of 70 and 40. kDa proteins from extracts of activated L3s than from non-activated L3s. We propose that an increase in Ac-hsb-1 levels early in activation allows feeding to resume, but that a subsequent decrease in expression permits a HSR that protects non-developing L3s at host-like temperatures. Further investigations of the HSR will clarify the role of HSB-1 and HSF-1 in hookworm infection. © 2010 Australian Society for Parasitology Inc.

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