Tyrosine Kinase signal modulation: A matter of H2O2 membrane permeability?

Milena Bertolotti, Stefano Bestetti, Jose M. García-Manteiga, Iria Medraño-Fernandez, Andrea Dal Mas, Maria Luisa Malosio, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

H2O2 produced by extracellular NADPH oxidases regulates tyrosine kinase signaling inhibiting phosphatases. How does it cross the membrane to reach its cytosolic targets? Silencing aquaporin-8 (AQP8), but not AQP3 or AQP4, inhibited H2O2 entry into HeLa cells. Re-expression of AQP8 with silencing-resistant vectors rescued H 2O2 transport, whereas a C173A-AQP8 mutant failed to do so. Lowering AQP8 levels affected H2O2 entry into the endoplasmic reticum, but not into mitochondria. AQP8 silencing also inhibited the H2O2 spikes and phosphorylation of downstream proteins induced by epidermal growth factor. These observations lead to the hypothesis that H2O2 does not freely diffuse across the plasma membrane and AQP8 and other H2O2 transporters are potential targets for manipulating key signaling pathways in cancer and degenerative diseases. Antioxid. Redox Signal. 19, 1447-1451.

Original languageEnglish
Pages (from-to)1447-1451
Number of pages5
JournalAntioxidants and Redox Signaling
Volume19
Issue number13
DOIs
Publication statusPublished - Nov 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry
  • Medicine(all)

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