| Popis: |
Dual specificity mitogen activated protein kinase phosphatase-1 (MKP-1) inactivates extracellular signal-regulated kinase (ERK), p38 and/or c-jun N-terminal protein kinase (JNK) by dephosphorylation via a negative feed-back loop. The aim of the present study was to assess the effectiveness, individually and in combination with the immunosuppressant agent FK506, of three structurally related monoperoxovanadium complexes on MKP-1 expression, on phosphorylation status of mitogen-activated protein kinase (MAPK), and on survival in PC12 cells. These compounds, known to be insulinomimetic agents and protein tyrosine phosphatase inhibitors, are cytotoxic to the cells, they activate JNK and down-regulate MPK-1. On the other hand, FK 506 has transient effect on ERK activation. However, when the agents are used in combination, MKP-1 expression is increased, and cell survival is enhanced. The concomitant alterations in the dynamic changes observed in signal intensities and duration of phospho-ERKs and phospho-JNKs signals suggest that in combination with monoperoxovanadium complexes, FK 506 enhances survival of PC12 cells by an induction of MKP-1 expression. |
