Hyperhomocysteinemia selectively alters expression and stoichiometry of intermediate filament and induces glutamate- and calcium-mediated mechanisms in rat brain during development.
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.
Loureiro
Samanta Oliveira
SO
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, CEP 90035-003 Porto Alegre, RS, Brazil.
Heimfarth
Luana
L
Pelaez
Priscila de Lima
Pde L
Lacerda
Bruna Arcce
BA
Vidal
Luiza Fedatto
LF
Soska
Angela
A
Santos
Natália Gomes Dos
NG
Andrade
Cláudia
C
Tagliari
Bárbara
B
Scherer
Emilene B S
EB
Guma
Fátima Therezinha Costa Rodrigues
FT
Wyse
Angela Terezinha de Souza
AT
Pessoa-Pureur
Regina
R
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
D007381:Intermediate Filament Proteins; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; D018698:Glutamic Acid; D002118:Calcium