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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Necrotic cells, %Two Short Peptides that Arise in Inflammation DemonstratedStrong Neuroprotective Effects In VitroVsevolod G. Pinelis 1 , Tatyana N. Storozhevykh 1 , Kristina V. Glebova 2 ,Tatyana N. Danyukova 2 , Yana E. Senilova 1 , Stanislav I. Schramm 2 ,and Nikolay F. Myasoedov 21 Laboratory of Membranology and Genetic Research, Scientific Center for ChildrenHealth, Russian Academy of Medical Sciences, Moscow, 119991, Russia; 2 Laboratory ofNeuropharmacology, Institute of Molecular Genetics, Russian Academy of Sciences,Moscow, 123182, RussiaIntroductionSeveral studies have shown that tripeptide N-acetyl-Pro-Gly-Pro (N-acetyl-PGP)endogenously derived from collagen or other extracellular matrix proteins is an importantmediator of inflammation in the lungs [1,2]. This activity is due to the ability of the peptideto activate neutrophils through chemokine receptors CXCR1 and CXCR2 [2]. Anotherpeptide, PGP, also demonstrated chemotactic activity, but weaker than N-acetyl-PGP [3]. Itis also known that cerebral ischemia progression in the brain leads to matrixmetalloproteinases activation and, perhaps, to accumulation of long-living products,especially Pro- and Gly-rich peptides [4]. Meanwhile, we have previously shown thatPGP-treatment has a neuroprotective effect after experimental focal brain ischemia in rats[5]. Based on these and some other data, we assume that ischemia-generated PGP-likepeptides can be actively involved both in inflammation and neuroprotection throughinteraction with neuronal or glial CXCR1/2. Thus, in this study we attempted to betterunderstand the nature of revealed neuroprotective effect using various in vitro models ofneuron damage, as well as cell cultures in which CXCR1/2 expression differs.Results and DiscussionTwo neuronal cell cultures one of which does not express CXCR1/2 (rat pheochromocytomaPC12 cell line) and the other one – well express CXCR1/2 (primary culture ofcerebellar granule neurons - CGNs) were used for modeling three different neuron damagemechanisms: 1) oxidative stress-stimulated necrosis (Oxidative stress model - PC12 cells,1 mM H 2 O 2 , 30 min); 2) growth factors deprivation-induced apoptosis (Deprivation model- CGNs, B-27 Supplements withdrawal, 24 h); and 3) glutamate receptor hyperactivation(Glu-toxicity model - CGNs, 100 μM Glu,1 h) resulting in both necrosis and100806040******PGPN-acetyl-PGP************200 0.1 1 10 100P e p t i d e, μMFig. 1. Cytoprotective effects of PGP andN-acetyl-PGP on neuronal PC12 cells afterH 2 O 2 -induced oxidative stress. ***p