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

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalMolecular and Cellular Biochemistry
Issue number1-2
StatePublished - Nov 2005

Bibliographical note

Funding Information:
This work was supported in part by Grants from NIH/NCI CA103180, CA094964, CA112557, and from NIH/NIEHS ES012451, ES00260. We thank Jane Galvin for secretarial support.


  • Calcium signaling
  • ERK
  • PI-3K
  • Vanadium
  • p38 kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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