Positive regulation of ERK activation and MKP-1 expression by peroxovanadium complex bpV (phen) |
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Authors: | L Rumora M Hadžija D Maysinger T Žanić-Grubišić |
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Institution: | (1) Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia;(2) Department of Molecular Medicine, Institute Ruder Bo kovi , Zagreb, Croatia;(3) Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada |
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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 mol/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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Keywords: | apoptosis mitogen-activated protein kinase mitogen-activated protein kinase phosphatase-1 peroxovanadium |
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