title: Hyperhomocysteinemia selectively alters expression and stoichiometry of intermediate filament and induces glutamate- and calcium-mediated mechanisms in rat brain during development.
abstract: The aim of the present work was to investigate the actions of a chemically induced chronic hyperhomocysteinemia model on intermediate filaments (IFs) of cortical and hippocampal neural cells and explore signaling mechanisms underlying such effects. Results showed that in hyperhomocysteinemic rats the expression of neural IF subunits was affected. In cerebral cortex, glial fibrillary acidic protein (GFAP) expression was donwregulated while in hippocampus high and middle molecular weight neurofilament subunits (NF-H and NF-M, respectively) were up-regulated. Otherwise, the immunocontent of IF proteins was unaltered in cerebral cortex while in hippocampus the immunocontent of cytoskeletal-associated low molecular weight neurofilament (NF-L) and NF-H subunits suggested a stoichiometric ratio consistent with a decreased amount of core filaments enriched in lateral projections. These effects were not accompanied by an alteration in IF phosphorylation. In vitro results showed that 500muM Hcy-induced protein phosphatases 1-, 2A- and 2B-mediated hypophosphorylation of NF subunits and GFAP in hippocampal slices of 17-day-old rats without affecting the cerebral cortex, showing a window of vulnerability of cytoskeleton in developing hippocampus. Ionotropic and metabotropic glutamate receptors were involved in this action, as well as Ca(2+) release from intracellular stores through ryanodine receptors. We propose that the mechanisms observed in the hippocampus of 17-day-old rats could support the neural damage observed in these animals.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Samanta Oliveira
authors.initials: SO
authors.lastname: Loureiro
authors.forename: Luana
authors.initials: L
authors.lastname: Heimfarth
authors.forename: Priscila de Lima
authors.initials: Pde L
authors.lastname: Pelaez
authors.forename: Bruna Arcce
authors.initials: BA
authors.lastname: Lacerda
authors.forename: Luiza Fedatto
authors.initials: LF
authors.lastname: Vidal
authors.forename: Angela
authors.initials: A
authors.lastname: Soska
authors.forename: Natália Gomes Dos
authors.initials: NG
authors.lastname: Santos
authors.forename: Cláudia
authors.initials: C
authors.lastname: Andrade
authors.forename: Bárbara
authors.initials: B
authors.lastname: Tagliari
authors.forename: Emilene B S
authors.initials: EB
authors.lastname: Scherer
authors.forename: Fátima Therezinha Costa Rodrigues
authors.initials: FT
authors.lastname: Guma
authors.forename: Angela Terezinha de Souza
authors.initials: AT
authors.lastname: Wyse
authors.forename: Regina
authors.initials: R
authors.lastname: Pessoa-Pureur
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; D018698:Glutamic Acid; D002118:Calcium