title: Exploratory investigation on nitro- and phospho-proteome cerebellum changes in hyperammonemia and hepatic encephalopathy rat models.
abstract: Hepatic encephalopathy (HE) is a neurological disease associated with hepatic dysfunction. Current knowledge suggests that hyperammonemia, related to liver failure, is a main factor contributing to the cerebral alterations in HE and that hyperammonemia might impair signal transduction associated with post-translational modification of proteins such as tyrosine-nitration and phosphorylation. However, the molecular bases of the HE remain unclear and very little is known about the occurrence of post-translational modification on in vivo proteins. In this exploratory study we look for evidence of post-translation modifications of proteins in the cerebellum of experimental HE rat models using a proteomic approach. For the first time we showed that hyperammonemia without liver failure (HA rats) and experimental HE with liver failure due to portacaval shunt (PCS rats) lead to a reduced protein nitration in rat cerebellum, where the undernitrated proteins were involved in energy metabolism and cytoskeleton remodelling. Moreover we showed that tyrosine nitration loss of these proteins was not necessarily associated to a change in their phosphorylation state as result of the disease. Interestingly the rat cerebellum phosphoproteome was mainly perturbed in PCS rats, whereas HA rats did not shown appreciable changes in their phosphoprotein profile. Since the protein nitration level decreased similarly in the cerebellum of both HA and PCS rats, this implies that the two disease models share common effects but also present some differential signalling effects in the cerebellum of the same animals. This study highlights the interest for studying the concerted action of multiple signalling pathways in HE development.
authors.affiliation: Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brunelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Campagna
authors.forename: Luisa
authors.initials: L
authors.lastname: Airoldi
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
authors.forename: Jordi
authors.initials: J
authors.lastname: Boix
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
mesh_terms: D000641:Ammonia / Q000009:adverse effects / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D022124:Hyperammonemia / Q000150:complications / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009574:Nitro Compounds / Q000378:metabolism; D010766:Phosphorylation; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D009574:Nitro Compounds; D014443:Tyrosine; D000641:Ammonia
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