Naslov
MKP-1 as a target for pharmacological manipulation in PC12 cell survival

Autori
Rumora, Lada ; Shaver, Alan ; Žanić-Grubišić, Tihana ; Maysingera, Dusica

Izvornik
Neurochemistry international (0197-0186) 39 (2001), 1; 25-32

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
peroxovanadium compounds; FK 506; MKP-1; MAPK; PC12 cells

Sažetak
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 role of expression of MKP-1 and phosphorylation status of mitogen-activated protein kinases (MAPKs) in promoting cell survival in PC12 cells. We used FK506 and three different monoperoxovanadium complexes (mpVs) as pharmacological tools for manipulation of MKP-1 expression. Peroxovanadium 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, ERK phosphorylation is prolonged and intensified, MKP-1 expression is increased, and cell survival is enhanced. The concomitant alterations observed in intensities and duration of phospho-ERKs and phospho-JNKs signals suggest that monoperoxovanadium complexes in combination with FK 506 enhance survival of PC12 cells by an induction of MKP-1 expression.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA