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Positive regulation of ERK activation and MKP-1 expression by peroxovanadium complex bpV (phen)

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Abstract

Lower micromolar concentrations of peroxovanadium compound potassium bisperoxo(1,10-phenanthroline)oxovanadate (V) [bpV (phen)] stimulate RINm5F cell metabolic activity. 1 and 3 μmol/L bpV (phen) induces strong and sustained activation of extracellular signal-regulated kinase (ERK). However, it seems that bpV (phen) does not effect c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In addition, bpV (phen) induces mitogen-activated protein kinase phosphatase-1 (MKP-1) expression. We found that ERK activation could be completely abolished if RINm5F cells were incubated with both bpV (phen) and PD 98059, a specific inhibitor of upstream ERK kinase MEK1. On the other hand, this combined treatment up-regulated activation of stress kinases, JNK and p38 MAPK, significantly suppressed MKP-1 expression and induced cell death. Thus, our results suggest that the mechanism underlying bpV (phen) survival-enhancing effect could be associated with induced ERK activation and MKP-1 expression.

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Authors and Affiliations

  1. Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia

    L. Rumora & T. Žanić-Grubišić

  2. Department of Molecular Medicine, Institute Ruder Bošković, Zagreb, Croatia

    M. Hadžija

  3. Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada

    D. Maysinger

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  1. L. Rumora
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  2. M. Hadžija
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  3. D. Maysinger
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  4. T. Žanić-Grubišić
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Rumora, L., Hadžija, M., Maysinger, D. et al. Positive regulation of ERK activation and MKP-1 expression by peroxovanadium complex bpV (phen). Cell Biol Toxicol 20, 293–301 (2004). https://doi.org/10.1007/s10565-004-5104-5

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  • DOI: https://doi.org/10.1007/s10565-004-5104-5

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