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ERKs activation and calcium signaling are both required for VEGF induction by vanadium in mouse epidermal Cl41 cells

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Abstract

The previous studies have demonstrated that vanadium exposure can cause a variety of biological effects. However, the mechanisms involved in the biological effects caused by vanadium are not well understood. Our previous studies have shown that exposure of mouse epidermal Cl 41 cells to vanadate stimulated the phosphorylation of both ERKs and p38K, and calcium signaling leading NFAT activation. In view of the evidence that ERKs and p38 kinase contribute to VEGF induction, we investigated in the present study the potential roles of ERKs, p38K, and calcium signaling in VEGF induction caused by vanadium exposure. Exposure of Cl 41 cells to vanadium led to VEGF induction in both time- and dose-dependent manners. Pre-treatment of Cl 41 cells with PD98059, an inhibitor of MEK1/2-ERKs pathway, but not SB202190, an inhibitor for p38K pathway, resulted in a dramatic inhibition of VEGF induction by vanadium. More interesting, pre-treatment of Cl 41 cells with intracellular calcium chelator, but not calcium channel blocker, resulted in a dramatic decrease in VEGF induction by vanadium. However, both PI-3K inhibitors and overexpression of Δp85, a dominant negative PI-3K mutant, resulted in only a marginal decrease in VEGF induction by vanadium. Moreover, mTOR, as a downstream molecule of PI-3K, did not attribute to VEGF induction by vanadium because rapamycin pre-treatment did not show any inhibitory effect on VEGF induction. These results indicate that ERKs and intracellular stored calcium release play a critical role in VEGF induction by vanadium. PI-3K is partially involved in VEGF induction by vanadium, while p38K and mTOR are not involved. Those results will help us to understand the molecular mechanisms involved in vanadium-induced biological effects.

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Abbreviations

DMBA:

7,12-dimethylbenz(a)anthracene

DMSO:

dimethyl sulfoxide

ERK:

extracellular signal-regulated kinases

FBS:

fetal bovine serum

HIF-1:

hypoxia-inducible Factor-1

JNK:

c-Jun N-terminal kinase

MAPK:

mitogen-activated protein kinase

MEM:

Eagle's minimal essential medium

mTOR:

mammalian target of rapamycin

PI-3K:

phosphotidylinositol 3-kinas

TGF-β:

transforming growth factor beta

TPA:

12-O-tetradecanoylphorbol-13-acetate

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Nelson Institute of Environmental Medicine, School of Medicine, New York University, Old Forge Road, Tuxedo, New York, USA

    Jingxia Li, Qiangsong Tong, Xianglin Shi, Max Costa & Chuanshu Huang

  2. Nelson Institute of Environmental Medicine, School of Medicine, New York University, 57 Old Forge Road, Tuxedo, NY, 10987, USA

    Chuanshu Huang

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Correspondence to Chuanshu Huang.

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Li, J., Tong, Q., Shi, X. et al. ERKs activation and calcium signaling are both required for VEGF induction by vanadium in mouse epidermal Cl41 cells. Mol Cell Biochem 279, 25–33 (2005). https://doi.org/10.1007/s11010-005-8212-5

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