The neuronal SAPK/JNK pathway is altered in a murine model of hyperhomocysteinemia
- 24 February 2004
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 89 (1) , 33-43
- https://doi.org/10.1046/j.1471-4159.2003.02297.x
Abstract
Deficiency in cystathionine beta synthase (CBS) leads to high plasma homocysteine concentrations and causes hyperhomocysteinemia, a common risk factor for vascular disease, stroke and possibly neurodegenerative diseases. Various neuronal diseases have been associated with hyperhomocysteinemia, but the molecular mechanisms of homocysteine toxicity are unknown. We investigated the pathways involved in the pathological process, by analyzing differential gene expression in neuronal tissues. We used a combination of differential display and cDNA arrays to identify genes differentially expressed during hyperhomocysteinemia in brain of CBS-deficient mice. In this murine model of hyperhomocysteinemia, both plasma and brain homocysteine concentrations were high. Several genes were found to be differentially expressed in the brains of CBS-deficient mice, and the identities of some of these genes suggested that the SAPK/JNK pathway was altered in the brains of CBS-deficient mice. We therefore investigated the activation of proteins involved in the SAPK/JNK cascade. JNK and c-Jun were activated in the hippocampal neurones of CBS-deficient mice, suggesting that the SAPK/JNK pathway may play an important role in the development of neuronal defects associated with hyperhomocysteinemia.Keywords
This publication has 56 references indexed in Scilit:
- Memantine in Moderate-to-Severe Alzheimer's DiseaseNew England Journal of Medicine, 2003
- Expression of the Cystathionine β Synthase (CBS) Gene During Mouse Development and Immunolocalization in Adult BrainJournal of Histochemistry & Cytochemistry, 2003
- Regulation of c‐Jun N‐terminal kinase, p38 kinase and AP‐1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotectionJournal of Neurochemistry, 2003
- Elevated plasma von Willebrand factor in a murine model of severe hyperhomocysteinemiaThrombosis and Haemostasis, 2003
- In the Cystathionine β-Synthase Knockout Mouse, Elevations in Total Plasma Homocysteine Increase Tissue S-Adenosylhomocysteine, but Responses of S-Adenosylmethionine and DNA Methylation Are Tissue SpecificJournal of Nutrition, 2002
- Endothelial Dysfunction and Elevation of S -Adenosylhomocysteine in Cystathionine β-Synthase–Deficient MiceCirculation Research, 2001
- Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid depositionHuman Molecular Genetics, 2001
- Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemiaJournal of Clinical Investigation, 2000
- A synaptic model of memory: long-term potentiation in the hippocampusNature, 1993
- Hyperhomocyst(e)inemia. A common and easily reversible risk factor for occlusive atherosclerosis.Circulation, 1990