Volume 272, Number 48, Issue of November 28, 1997 pp. 30400-30404
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Thioredoxin Is Transcriptionally Induced upon Activation of Heat Shock Factor 2

(Received for publication, June 30, 1997)

Sirpa Leppä , Lila Pirkkala , Sek C. Chow , John E. Eriksson and Lea Sistonen

From the  Turku Centre for Biotechnology, University of Turku, Åbo Akademi University, FIN-20521 Turku, Finland, the  Department of Biology, Åbo Akademi University, BioCity, FIN-20521 Turku, Finland, and the  Center for Mechanism of Human Toxicity, University of Leicester, Leicester LE1 9HN, United Kingdom

Heat shock gene expression is differentially regulated in cells exposed to stress stimuli and in cells undergoing processes of differentiation and development. Regulation of the classical heat shock response is mediated by heat shock factor 1 (HSF1), whereas heat shock factor 2 (HSF2) is activated in certain differentiating cells, for example during hemin-mediated differentiation of human K562 erythroleukemia cells. Hence, the signaling pathways leading to induction of heat shock gene expression upon different stimuli are likely to be distinct. We have used RNA arbitrarily primed polymerase chain reaction to identify genes that are differentially regulated upon activation of HSF1 and HSF2. In this study, we report that thioredoxin (TRX) expression is induced in K562 cells in response to hemin in an HSF2-dependent manner. Increased TRX expression was primarily detected on the transcriptional level, subsequently leading to elevated TRX mRNA and protein levels. Hemin treatment caused no reduction in cellular glutathione concentrations, indicating that the increased TRX expression was not due to oxidative stress. Studies using cell lines where overexpression of the HSF2- isoform represses HSF2 activation implied that active HSF2 is required for transcriptional induction of TRX. Unlike HSF2, activation of HSF1 did not induce TRX expression. Taken together, our results suggest that HSF1 and HSF2 may regulate distinct target genes, and activation of HSF2 could be involved in the regulation of TRX expression during hemin-mediated differentiation of K562 cells.

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