VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

García-Román, Jonathan; Ibarra-Sánchez, Alfredo; Lamas, Marta; González-Espinosa, Claudia

doi:10.1016/j.bbrc.2010.09.047

Cited by 20 publications

(17 citation statements)

References 33 publications

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“…Mast cell tryptase and chymase are angiogenic (Ribatti et al, 2011). VEGF secretion during hypoxia requires mast cells (García-Román et al, 2010). Mast cells play essential role for angiogenesis in cervical carcinogenesis (Utrera-Barillas et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

DNA methyl transferase I acts as a negative regulator of allergic skin inflammation

Kim

Park

et al. 2013

Molecular Immunology

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Section: Discussionmentioning

confidence: 99%

DNA methyl transferase I acts as a negative regulator of allergic skin inflammation

Kim

Park

et al. 2013

Molecular Immunology

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“…Interestingly, although only the overexpression of VAMP8 functionally interfered with Rab5-mediated fusion, VAMP2, VAMP3, and VAMP7 also localized to the SGs. Therefore, whereas VAMP8 is presumably directly involved in mediating the homotypic SG fusion, VAMP2, VAMP3, VAMP7, and possibly also VAMP8 itself might be involved in the SG fusion with the plasma membrane or the endocytic system (49)(50)(51)(52). In particular, interactions with the endocytic system might be amplified in cells expressing the CA Rab5A mutant.…”

Section: Discussionmentioning

confidence: 99%

“…Because vesicle fusion depends on the precise coupling of the SNARE proteins that zipper into stable membrane-bridging (trans) complexes, overexpression of a relevant SNARE may disturb the fusion process (47)(48)(49). Therefore, we overexpressed members of the VAMP family that were previously implicated in playing a role in mast cell exocytosis (49)(50)(51)(52)(53) and analyzed their impact on the Rab5-stimulated enlargement of SGs. Consistent with their implicated role in controlling mast cell exocytosis (49,53), VAMP2, VAMP3, VAMP7, and VAMP8 colocalized with NPY-mRFP in the SGs of the CA Rab5A-expressing cells (Supplemental Fig.…”

Section: Overexpressed Vamp8 Inhibits Rab5-mediated Fusion and Conseqmentioning

confidence: 99%

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Azouz

Zur

Efergan

et al. 2014

The Journal of Immunology

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Secretion of inflammatory mediators prestored in mast cells secretory granules (SGs) enhances immune responses such as in allergy and host defense. However, the mechanisms underlying the biogenesis of the SGs remain largely unresolved. By combining high-resolution live cell imaging and quantitative morphometric analyses, we show that the small GTPase Rab5 controls the SG size and cargo composition by a VAMP8-dependent fusion mechanism. Knockdown of the endogenous Rab5, or expression of constitutively negative mutants, significantly reduces the size of SGs and increases their number. Conversely, expression of constitutively active Rab5 mutants induces few, but giant, SGs. Both the small and giant SGs maintain their exocytosis competence. Finally, we show that Rab5-mediated fusion between Golgi-derived SGs and early endosomes precedes the maturation of the SGs, as reflected by the recruitment of Rab27B, and allows the incorporation of cargo, such as CD63, that traffics through endosomes. Collectively, our results assign Rab5 a key role in mediating mast cell SG fusion during biogenesis, thereby controlling the amount and composition of the SGs content and maintaining the communication between new and pre-existing SGs.

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“…In bone marrow mast cells, for example, hypoxia, as assessed through cell treatment with the hypoxic mimetic agent cobalt chloride, was demonstrated to increase VEGF production through a mechanism dependent on ROS formation [49]. Similarly, Brown et al [46] reported HIF-1α-dependent secretion of VEGF from bladder carcinoma cells exposed to hypoxia during treatment with thymidine phosphorylase, an enzyme which up-regulates the expression of markers of oxidative stress.…”

Section: Influence Of the Hypoxia-ros-hif-1α Pathway On Tumorigenesismentioning

confidence: 99%

Hypoxia and free radicals: Role in tumor progression and the use of engineering-based platforms to address these relationships

Hielscher

Gerecht

2015

Free Radical Biology and Medicine

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Hypoxia is a feature of all solid tumors, contributing to tumor progression and therapy resistance. Through stabilization of the hypoxia-inducible factor 1 alpha (HIF-1α), hypoxia activates the transcription of a number of genes which sustain tumor progression. Since the seminal discovery of HIF-1α as a hypoxia-responsive master regulator of numerous genes and transcription factors, several groups have reported a novel mechanism whereby hypoxia mediates stabilization HIF-1α. This process occurs as a result of hypoxia generated reactive oxygen species (ROS), which in turn, stabilize the expression of HIF-1α. As a result, a number of genes regulating tumor growth are expressed, fueling ongoing tumor progression. In this review, we outline a role for hypoxia in generating ROS and additionally define the mechanisms contributing to ROS-induced stabilization of HIF-1α.We further explore how ROS-induced HIF-1α stabilization contribute to tumor growth, angiogenesis, metastasis and therapy response. We discuss a future outlook, describing novel therapeutic approaches for attenuating ROS production while considering how these strategies should be carefully selected when combining with chemotherapeutic agents. As engineering-based approaches have been more frequently utilized to address biological questions, we discuss opportunities whereby engineering techniques may be employed to better understand the physical and biochemical factors controlling ROS expression. It is anticipated that an improved understanding of the mechanisms responsible for the hypoxia/ROS/HIF-1α axis in tumor progression will yield the development of better targeted therapies.

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VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

Cited by 20 publications

References 33 publications

DNA methyl transferase I acts as a negative regulator of allergic skin inflammation

DNA methyl transferase I acts as a negative regulator of allergic skin inflammation

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Hypoxia and free radicals: Role in tumor progression and the use of engineering-based platforms to address these relationships

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