On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure.
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 50-200mg/kg linamarin, or 200mg/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. α-spectrin). Studies are needed to elucidate the role of the aformentioned modifications in the pathogenesis of cassava-associated motor-system disease.
Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR, USA.
Roman M
RM
Kassa
Nyamabo L
NL
Kasensa
Victor H
VH
Monterroso
Robert J
RJ
Kayton
John E
JE
Klimek
Larry L
LL
David
Kalala R
KR
Lunganza
Kazadi T
KT
Kayembe
Marina
M
Bentivoglio
Sharon L
SL
Juliano
Desire D
DD
Tshala-Katumbay
D000595:Amino Acid Sequence; D000603:Amino Acids, Sulfur / Q000172:deficiency; D000818:Animals; D015415:Biomarkers; D003485:Cyanates / Q000032:analysis; D004032:Diet; D008297:Male; D002365:Manihot / Q000737:chemistry*; D016472:Motor Neuron Disease / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D009570:Nitriles / Q000633:toxicity*; D020543:Proteome / Q000032:analysis; D051381:Rats; D011923:Rats, Nude; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013861:Thiocyanates / Q000032:analysis; D057825:Two-Dimensional Difference Gel Electrophoresis
D000603:Amino Acids, Sulfur; D015415:Biomarkers; D003485:Cyanates; D009570:Nitriles; D020543:Proteome; D013861:Thiocyanates; C011206:cyanogen; C009281:sodium cyanate; C005091:linamarin; C031760:thiocyanate