期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 49, 期 3, 页码 571-578出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2010.05.080
关键词
Biomarkers; Cassava; Cyanate; Konzo; Linamarin; Proteomics
资金
- NIEHS [R21ES017225]
- NINDS [K01NS052183]
- National Institutes of Health (Bethesda, MD) [5P30CA069533, 5P30EY010572, P30NS061800]
Konzo is a self-limiting central motor-system disease associated with food dependency on cassava and low dietary intake of sulfur amino acids (SAA). Under conditions of SAA-deficiency, ingested cassava cyanogens yield metabolites that include thiocyanate and cyanate, a protein-carbamoylating agent. We studied the physical and biochemical modifications of rat serum and spinal cord proteins arising from intoxication of young adult rats with 50-200 mg/kg linamarin, or 200 mg/kg sodium cyanate (NaOCN), or vehicle (saline) and fed either a normal amino acid- or SAA-deficient diet for up to 2 weeks. Animals under SAA-deficient diet and treatment with linamarin or NaOCN developed hind limb tremors or motor weakness, respectively. LC/MS-MS analysis revealed differential albumin carbamoylation in animals treated with NaOCN, vs. linamarin/SAA-deficient diet, or vehicle. 2D-DIGE and MALDI-TOF/MS-MS analysis of the spinal cord proteome showed differential expression of proteins involved in oxidative mechanisms (e.g. peroxiredoxin 6), endocytic vesicular trafficking (e.g. dynamin 1), protein folding (e.g. protein disulfide isomerase), and maintenance of the cytoskeleton integrity (e.g. alpha-spectrin). Studies are needed to elucidate the role of the aformentioned modifications in the pathogenesis of cassava-associated motor-system disease. (C) 2010 Elsevier Ltd. All rights reserved.
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