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 language | English |
|---|---|
| Pages (from-to) | 1447-1451 |
| Number of pages | 5 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 19 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Nov 1 2013 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Physiology
- Clinical Biochemistry
- Medicine(all)
Cite this
Tyrosine Kinase signal modulation : A matter of H2O2 membrane permeability? / Bertolotti, Milena; Bestetti, Stefano; García-Manteiga, Jose M.; Medraño-Fernandez, Iria; Dal Mas, Andrea; Malosio, Maria Luisa; Sitia, Roberto.
In: Antioxidants and Redox Signaling, Vol. 19, No. 13, 01.11.2013, p. 1447-1451.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tyrosine Kinase signal modulation
T2 - A matter of H2O2 membrane permeability?
AU - Bertolotti, Milena
AU - Bestetti, Stefano
AU - García-Manteiga, Jose M.
AU - Medraño-Fernandez, Iria
AU - Dal Mas, Andrea
AU - Malosio, Maria Luisa
AU - Sitia, Roberto
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84882657620&partnerID=8YFLogxK
U2 - 10.1089/ars.2013.5330
DO - 10.1089/ars.2013.5330
M3 - Article
C2 - 23541115
AN - SCOPUS:84882657620
VL - 19
SP - 1447
EP - 1451
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 13
ER -