title: Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance to the biomarkers of cassava cyanogenesis and motor system toxicity.
abstract: 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.
authors.affiliation: Department of Pharmacology and Pharmacognosy, University of Nairobi, Nairobi, 19676 Kenya ; School of Nursing Sciences, University of Nairobi, Nairobi, 19676 Kenya.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kimani
authors.affiliation: Department of Comparative Medicine, Oregon Health & Science University (OHSU), Portland, OR 97239 USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Moterroso
authors.affiliation: Center for Research on Occupational & Environmental Toxicology, OHSU, Portland, OR 97239 USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Lasarev
authors.affiliation: Department of Pharmacology and Pharmacognosy, University of Nairobi, Nairobi, 19676 Kenya.
authors.forename: Sinei
authors.initials: S
authors.lastname: Kipruto
authors.affiliation: Department of Medical Physiology, University of Nairobi, Nairobi, 30197 Kenya.
authors.forename: Fred
authors.initials: F
authors.lastname: Bukachi
authors.affiliation: Department of Pharmacology and Pharmacognosy, University of Nairobi, Nairobi, 19676 Kenya.
authors.forename: Charles
authors.initials: C
authors.lastname: Maitai
authors.affiliation: Biochemistry and Molecular Biology & Proteomics Shared Resource, OHSU, Portland, OR 97239 USA.
authors.forename: Larry
authors.initials: L
authors.lastname: David
authors.affiliation: Center for Research on Occupational & Environmental Toxicology, OHSU, Portland, OR 97239 USA ; Department of Neurology, OHSU, Portland, OR 97239 USA ; Center for Research on Occupational and Environmental Toxicology & Department of Neurology, Oregon Health & Science University, 3181 Sam Jackson Park Road, Mail code L606, Portland, OR 97239 USA.
authors.forename: Desire
authors.initials: D
authors.lastname: Tshala-Katumbay
keywords: Carbamoylation; Cyanate; Cyanide; Neuropathy; Proteomics