| First Author | García-Román J | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 401 |
| Issue | 2 | Pages | 262-7 |
| PubMed ID | 20850416 | Mgi Jnum | J:165846 |
| Mgi Id | MGI:4838685 | Doi | 10.1016/j.bbrc.2010.09.047 |
| Citation | Garcia-Roman J, et al. (2010) VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells. Biochem Biophys Res Commun 401(2):262-7 |
| abstractText | Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl2) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl2 promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl2-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl2-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl2 in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals-dependent Fyn kinase activation. |
