Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not hydrogen peroxide production

Feng Chen, Deepesh Pandey, Ahmed Chadli, John D. Catravas, Teng Chen, David J Fulton

Research output: Contribution to journalArticle

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Abstract

The goal of this study was to identify whether heat-shock protein 90 (Hsp90) regulates the production of superoxide and other reactive oxygen species from the NADPH oxidases (Nox). We found that pharmacological and genetic inhibition of Hsp90 directly reduced Nox5-derived superoxide without secondarily modifying signaling events. Coimmunoprecipitation and bioluminescence resonance energy transfer studies suggest that the C-terminus of Nox5 binds to Hsp90. Long-term Hsp90 inhibition reduced Nox5 expression and provides further evidence that Nox5 is an Hsp90 client protein. Inhibitors of Hsp90 also reduced superoxide from Nox1, Nox2 (neutrophils), and Nox3. However, Nox4, which emits only hydrogen peroxide, was unaffected by Hsp90 inhibitors. Hydrogen peroxide production from the other Nox enzymes was not affected by short-term inhibition of Hsp90, but long-term inhibition reduced production of all reactive oxygen species coincident with loss of enzyme expression. Expression of chimeric Nox enzymes consisting of N-terminal Nox1 or Nox3 and C-terminal Nox4 resulted in only hydrogen peroxide formation that was insensitive to Hsp90 inhibitors. We conclude that Hsp90 binds to the C-terminus of Noxes1-3 and 5 and is necessary for enzyme stability and superoxide production. Hsp90 does not bind to the C-terminus of Nox4 and is not required for hydrogen peroxide formation.

Original languageEnglish (US)
Pages (from-to)2107-2119
Number of pages13
JournalAntioxidants and Redox Signaling
Volume14
Issue number11
DOIs
StatePublished - Jun 1 2011

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HSP90 Heat-Shock Proteins
NADPH Oxidase
Superoxides
Hydrogen Peroxide
Enzymes
Reactive Oxygen Species
Bioluminescence
Enzyme Stability
Energy Transfer
Energy transfer
Neutrophils

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not hydrogen peroxide production. / Chen, Feng; Pandey, Deepesh; Chadli, Ahmed; Catravas, John D.; Chen, Teng; Fulton, David J.

In: Antioxidants and Redox Signaling, Vol. 14, No. 11, 01.06.2011, p. 2107-2119.

Research output: Contribution to journalArticle

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