cGMP-dependent protein kinase is involved in cPLA2 phosphorylation, AA release and cell death in in vivo and in vitro modelsvof 1-methyl-4-phenylpyridinium-induced parkinsonism

• Autorzy: Chalimoniuk M. , Stolecka A. , Zieminska E. , Stepien A. , Langfort J. , Strosznajder J.B.
• Języki publikacji: EN

Abstrakty

EN

We investigated if the cGMP/cCGP-dependent protein kinase (PKG) signaling pathway was involved in 1-methyl-4-phenylpyridinium (MPP+)-induced cPLA2 activation of dopaminergic neuronal cells (PC12 cells). We found increased levels of total and phosphorylated cPLA2 and increased AA release in the nigrostriatal system of MPTPinduced parkinsonism mice and in PC12 cells exposed to MPP+. We used cPLA2-specifi c inhibitors and Ca2+-independent PLA2 (iPLA2), and we found that cPLA2 released more AA after stimulation with MPTP/MPP+ than iPLA2 and that there was a time-dependent delay of AA release by iPLA2 compared to cPLA2. The PKG inhibitor KT5823 decreased MPTP-induced AA release in the nigrostriatal pathway. KT5823, in addition to PKC and ERK1/2 inhibitors, decreased cPLA2 activity as well as total and phosphorlyated cPLA2 protein levels in the midbrain and striatum of MPTP-induced parkinsonism mice. Inhibition occurred within 30 minutes and persisted for up to 24 hours. Similar results were also observed in MPP+-treated PC12 cells. Dual treatment with PKG and PKC inhibitors had the same effect on cPLA2 activity and protein levels. PKG is involved in the enhancement of cPLA2 phosphorylation at Serine-505 and in AA release in PC12 cells exposed to MPP+. In PC12 cells, inhibitors of cPLA2 and PKG increased viability and prevented MPP+-induced apoptosis. Our results indicate that the nNOS/cGMP/PKG pathway stimulates cPLA2 phosphorylation at Ser-505 by activation of PKC or ERK1/2. Our results also suggest that upregulation of the nNOS/cGMP pathway observed in experimental models of PD may mediate dopaminergic neuron degeneration and death through activation of cPLA2. This work was supported by MSHE, Scientifi c Network nr. 28/E32/SN-0053/2007

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.102

Twórcy

autor

Chalimoniuk M.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Stolecka A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
• Department of Physiology, Academy of Physical Education, Katowice, Poland

autor

Zieminska E.

• Department of Neurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland;

autor

Stepien A.

• Department of Neurology, Military Institute of the Health Services, Warsaw, Poland

autor

Langfort J.

• Department of Physiology, Academy of Physical Education, Katowice, Poland
• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Strosznajder J.B.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland