Homocysteine activates calcium‐mediated cell signaling mechanisms targeting the cytoskeleton in rat hippocampus

Homocysteine is considered to be neurotoxic and a risk factor for neurodegenerative diseases. Despite the increasing evidences of excitotoxic mechanisms of homocysteine (Hcy), little is known about the action of Hcy on the cytoskeleton. In this context, the aim of the present work was to investigate...

Full description

Saved in:
Bibliographic Details
Published in:International journal of developmental neuroscience 2008-08, Vol.26 (5), p.447-455
Main Authors: Loureiro, Samanta Oliveira, Heimfarth, Luana, Pelaez, Priscila de Lima, Vanzin, Camila Simioni, Viana, Lilian, Wyse, Angela T.S., Pessoa‐Pureur, Regina
Format: Article
Language:English
Subjects:
Animals
Benzylamines - pharmacology
Calcium - metabolism
Calcium Signaling - drug effects
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Cell signaling
Cyclic AMP - metabolism
Cytoskeleton - drug effects
Cytoskeleton - metabolism
Flavonoids - pharmacology
Hippocampus
Hippocampus - drug effects
Hippocampus - metabolism
Homocysteine
Homocysteine - pharmacology
Inositol Phosphates - metabolism
Intermediate filaments
Intermediate Filaments - metabolism
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Models, Biological
Phosphorylation
Phosphorylation - drug effects
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
Rats
Receptors, N-Methyl-D-Aspartate - metabolism
Ryanodine Receptor Calcium Release Channel - metabolism
Signal Transduction - drug effects
Staurosporine - pharmacology
Sulfonamides - pharmacology
Type C Phospholipases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Homocysteine is considered to be neurotoxic and a risk factor for neurodegenerative diseases. Despite the increasing evidences of excitotoxic mechanisms of homocysteine (Hcy), little is known about the action of Hcy on the cytoskeleton. In this context, the aim of the present work was to investigate the signaling pathways involved in the mechanism of action of Hcy on cytoskeletal phosphorylation in cerebral cortex and hippocampus of rats during development. Results showed that 100 μM Hcy increased the intermediate filament (IF) phosphorylation only in 17‐day‐old rat hippocampal slices without affecting the cerebral cortex from 9‐ to 29‐day‐old animals. Stimulation of 45Ca2+ uptake supported the involvement of NMDA receptors and voltage‐dependent channels in extracellular Ca2+ flux, as well as Ca2+ release from intracellular stores through inositol‐3‐phosphate and ryanodine receptors. Moreover, the mechanisms underlying the Hcy effect on hippocampus cytoskeleton involved the participation of phospholipase C, protein kinase C, mitogen‐activated protein kinase, phosphoinositol‐3 kinase and calcium/calmodulin‐dependent protein kinase II. The Hcy‐induced IF hyperphosphorylation was also related to Gi protein and inhibition of cAMP levels. These findings demonstrate that Hcy at a concentration described to induce neurototoxicity activates the IF‐associated phosphorylating system during development in hippocampal slices of rats through different cell signaling mechanisms. These results probably suggest that hippocampal rather than cortical cytoskeleton is succeptible to neurotoxical concentrations of Hcy during development and this could be involved in the neural damage characteristic of mild homocystinuric patients.
ISSN:0736-5748
1873-474X
DOI:10.1016/j.ijdevneu.2008.03.001