Involvement of multiple protein kinases in cPLA2 phosphorylation, AA release and cell death in astrocyte treated with 1-methyl-4-phenylpyridinium-the possible key role of PKG

• Autorzy: Chalimoniuk M. , Stolecka A. , Gabryel B. , Malecki A. , Langfort J.
• Języki publikacji: EN

Abstrakty

EN

Cytosolic phospholipase A2 (cPLA2) demonstrates selective affi nity to arachidonic acid (AA) liberation, which is known to be elevated in PD. We indicated that NO/GC/cGMP pathway was upregulated in the primary astrocyte culture treated with MPP+. We investigated if the cGMP/cGMP-dependent protein kinase (PKG) signaling pathway was involved in 1-methyl-4-phenylpyridinium (MPP+)-induced cPLA2 activation of the primary astrocyte culture. We found increased levels of total and phosphorylated cPLA2 and increased AA release in the primary astrocyte culture 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 MPP+ than iPLA2 and that there was a time-dependent delay of AA release by iPLA2 compared to cPLA2. The PKG inhibitor KT5823 decreased MPP-induced AA release in the primary astrocyte culture. KT5823, in addition to PKC and ERK1/2 inhibitors, decreased cPLA2 activity as well as total and phosphorylated cPLA2 protein levels in the astrocyte treated with MPP+. Dual treatment with PKG and PKC or ERK1/2 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 the astrocyte exposed to MPP+. Our results indicate that the nNOS/cGMP/ PKG pathway stimulates cPLA2 phosphorylation at Ser-505 by activation of PKC or ERK1/2. These results suggest that activation of cPLA2 by upregulation nNOS/cGMP pathway may play important role in MPP+-induced astrocyte activation, neurotoxicity and oxidative stress in the nigrostriatal system.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.101

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

Gabryel B.

• Department of Pharmacology, Medical University of Silesia, Katowice, Poland

autor

Malecki A.

• Department of Pharmacology, Medical University of Silesia, Katowice, Poland

autor

Langfort J.

• Department of Pharmacology, Medical University of Silesia, Katowice, Poland
• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland