TAK1 promotes cell survival by TNFAIP3 and IL-8 dependent and NF-kB independent pathway in HeLa cells exposed to heat stress

Peng Li, Yukihiro Furusawa, Zheng Li Wei, Hiroaki Sakurai, Yoshiaki Tabuchi, Qing Li Zhao, Ikuo Saiki, Takashi Kondo

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Purpose: Transforming growth factor-b-activated kinase 1 (TAK1) plays a role in inhibiting apoptosis in response to multiple stresses. In the present study, we investigated the role of TAK1 in cell death induced by heat stress (HS). Materials and methods: TAK1 knockdown HeLa cells and their parental cells were exposed to HS at 44°C for 15, 30, 45 min followed by colony formation assay. Heat shock proteins (HSPs) induction, NF-kB phosphorylation, and caspase-3 cleavage were estimated by western blotting using specific antibodies. Global gene expression analysis was performed using the GeneChip® system. The anti-apoptotic roles of the identified genes were elucidated using small interfering RNAs targeting those genes. Results: Heat sensitivity estimated by colony formation assay and caspase-3 cleavage increased in TAK1 knockdown cells. This sensitisation was not due to alterations in HSP induction or NF-kB phosphorylation as the expression levels of these proteins did not differ significantly between the TAK1 knockdown and the parent cells after HS exposure. The GeneChip® analysis revealed differences in gene expression between both cell variants after HS exposure and defined the genetic network associated with cell death. TNF-a interacting protein 3 (TNFAIP3) and Interleukin 8 (IL-8) are two of the identified genes. RNA interference against these genes increased the cleavage of caspase-3 and cell death after HS exposure. Conclusion: Our findings reveal the role of TAK1 in thermoresistance and show that the mediation is independent of NF-kB phosphorylation but is dependent on TNFAIP3 and IL-8 induction.

Original languageEnglish
Pages (from-to)688-695
Number of pages8
JournalInternational Journal of Hyperthermia
Volume29
Issue number7
DOIs
Publication statusPublished - 2013 Jan 1

Keywords

  • Hyperthermia
  • IL-8
  • TAK1
  • TNFAIP3
  • microarray

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cancer Research

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