TY - JOUR
T1 - Carbamoylation correlates of cyanate neuropathy and cyanide poisoning
T2 - Relevance to the biomarkers of cassava cyanogenesis and motor system toxicity
AU - Kimani, Samuel
AU - Moterroso, Victor
AU - Lasarev, Mike
AU - Kipruto, Sinei
AU - Bukachi, Fred
AU - Maitai, Charles
AU - David, Larry
AU - Tshala-Katumbay, Desire
N1 - Funding Information:
This work as supported by supported by the National Institutes of Health, Bethesda, MD [NIEHS and FIC grants number R21ES017225 and R01ES019841]; and a fellowship from the International Society for Neurochemistry/Committee for Aid and Education in Neurochemistry to Samuel Kimani. Laboratory animals were donated by Professor Neuwelt, Department of Neurology, Oregon Health & Science University (OHSU).
PY - 2013
Y1 - 2013
N2 - We sought to elucidate the protein carbamoylation patterns associated with cyanate neuropathy relative to cyanide poisoning. We hypothesized that under a diet deficient in sulfur amino acids (SAA), the carbamoylation pattern associated with cyanide poisoning is similar to that of cyanate neuropathy. Male rats (6-8 weeks old) were fed a diet with all amino acids (AAA) or 75%-deficiency in SAA and treated with 2.5 mg/kg/body weight (bw) NaCN, or 50 mg/kg/bw NaOCN, or 1 μl/g/bw saline, for up to 6 weeks. Albumin and spinal cord proteins were analyzed using liquid chromatography mass spectrometry (LC-MS/MS). Only NaOCN induced motor deficits with significant levels of carbamoylation. At Day 14, we found a diet-treatment interaction effect on albumin carbamoylation (p = 0.07). At Day 28, no effect was attributed to diet (p = 0.71). Mean number of NaCN-carbamoylated sites on albumin was 47.4% higher relative to vehicle (95% CI:16.7-86.4%). Only NaOCN carbamoylated spinal cord proteins, prominently, under SAA-restricted diet. Proteins targets included myelin basic and proteolipid proteins, neurofilament light and glial fibrillary acidic proteins, and 2', 3' cyclic-nucleotide 3'-phosphodiesterase. Under SAA deficiency, chronic but not acute cyanide toxicity may share biomarkers and pathogenetic similarities with cyanate neuropathy. Prevention of carbamoylation may protect against the neuropathic effects of cyanate.
AB - We sought to elucidate the protein carbamoylation patterns associated with cyanate neuropathy relative to cyanide poisoning. We hypothesized that under a diet deficient in sulfur amino acids (SAA), the carbamoylation pattern associated with cyanide poisoning is similar to that of cyanate neuropathy. Male rats (6-8 weeks old) were fed a diet with all amino acids (AAA) or 75%-deficiency in SAA and treated with 2.5 mg/kg/body weight (bw) NaCN, or 50 mg/kg/bw NaOCN, or 1 μl/g/bw saline, for up to 6 weeks. Albumin and spinal cord proteins were analyzed using liquid chromatography mass spectrometry (LC-MS/MS). Only NaOCN induced motor deficits with significant levels of carbamoylation. At Day 14, we found a diet-treatment interaction effect on albumin carbamoylation (p = 0.07). At Day 28, no effect was attributed to diet (p = 0.71). Mean number of NaCN-carbamoylated sites on albumin was 47.4% higher relative to vehicle (95% CI:16.7-86.4%). Only NaOCN carbamoylated spinal cord proteins, prominently, under SAA-restricted diet. Proteins targets included myelin basic and proteolipid proteins, neurofilament light and glial fibrillary acidic proteins, and 2', 3' cyclic-nucleotide 3'-phosphodiesterase. Under SAA deficiency, chronic but not acute cyanide toxicity may share biomarkers and pathogenetic similarities with cyanate neuropathy. Prevention of carbamoylation may protect against the neuropathic effects of cyanate.
KW - Carbamoylation
KW - Cyanate
KW - Cyanide
KW - Neuropathy
KW - Proteomics
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U2 - 10.1186/2193-1801-2-647
DO - 10.1186/2193-1801-2-647
M3 - Article
AN - SCOPUS:84891385405
SN - 2193-1801
VL - 2
SP - 1
EP - 8
JO - SpringerPlus
JF - SpringerPlus
IS - 1
M1 - 647
ER -