title: Can proline-rich polypeptide complex mimic the effect of nerve growth factor?
abstract: Naturally occurring compounds that can act as prosurvival factors and neurite formation stimulants in the conditions of reduced neurotrophins production are important both in neuronal protection and therapy of neurodegenerative disorders. Therefore, the role of proline-rich polypeptide complex (PRP) and its nonapeptide fragment (NP) in the promotion of pheochromocytoma cell line (PC12) survival and neurite outgrowth pathway is presented. It was shown that PRP/NP did not affect the neuronal nitric oxide synthase (nNOS) at the transcriptional and protein level. However, the activity of nNOS and intracellular nitric oxide (NO) concentration was markedly increased after treatment of PC12 cells with peptides. This reaction was inhibited by L-NAME-nNOS inhibitor. It was shown that PRP and NP induce the soluble guanylyl cyclase to release higher amount of cyclic GMP (cGMP), and subsequently, the increased phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) is observed. This effect was abolished by both U0126 (inhibitor of ERK1/2) and also by L-NAME. Reduction of ERK1/2 activity observed in the presence of nNOS inhibitor suggests that its activation is NO-dependent. The presented results shed some light on the mechanism of action of PRP complex. PRP and NP can activate NO/cGMP/ERK1/2 signaling pathway, similarly to nerve growth factor (NGF). The prosurvival action and short fibers formation suggest the role of PRP and NP in neuroprotection and the initiation of neuritogenesis. They can also participate in the amplification of signals controlling the survival and differentiation of neurons effect when the deficit of NGF takes place.
authors.affiliation: Department of Immunochemistry, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zabłocka
authors.forename: Anna
authors.initials: A
authors.lastname: Urbaniak
authors.forename: Marianna
authors.initials: M
authors.lastname: Kuropatwa
authors.forename: Joanna
authors.initials: J
authors.lastname: Zyzak
authors.forename: Joanna
authors.initials: J
authors.lastname: Rossowska
authors.forename: Maria
authors.initials: M
authors.lastname: Janusz
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018716:Molecular Mimicry; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D016716:PC12 Cells; D010455:Peptides / Q000494:pharmacology*; D055232:Proline-Rich Protein Domains; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D052248:Nitric Oxide Synthase Type I; D048049:Extracellular Signal-Regulated MAP Kinases; D006152:Cyclic GMP
keywords: ERK1/2 kinases; cyclic GMP; nerve growth factor; nitric oxide; nonapeptide (NP); proline-rich polypeptide complex (PRP)