Acetyl-CoA synthetase, NADP malate dehydrogenase and ATP citrate lyase in the degenerating peripheral nerve

Bonavita, V.; Piccoli, Federico; Serra, Salvatore

doi:10.1016/0006-8993(68)90127-3

Cited by 1 publication

(1 citation statement)

References 18 publications

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“…Proteins or enzymes associated with energy metabolism have been previously implicated in the genesis of c-diketone axonopathy (Sabri et al, 1979;Sabri, 1984) and were well represented (ACLY, Hadha, ODP2, Pkm2, Hmgcs1, Ndufa10, and Gpd) among the 22 proteins studied here. ACLY activity was proposed as a biomarker of Wallerian degeneration in peripheral nerves in the late 60#s (Bonavita et al, 1968). Pkm2 and Hadha, a subunit of the mitochondrial trifunctional protein (TFP), may also be of interest because mutations in the genes encoding for TFP subunits and oxidative damage of pkm2 have been respectively implicated in systemic organ failure associated with encephalopathy and mild cognitive impairment in aging subjects (Butterfield et al, 2006;Choi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Probing Mechanisms of Axonopathy. Part I: Protein Targets of 1,2-Diacetylbenzene, the Neurotoxic Metabolite of Aromatic Solvent 1,2-Diethylbenzene

Tshala-Katumbay

Monterroso²,

Kayton

et al. 2008

Toxicological Sciences

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Motor neuron axonopathy in diseases such as amyotrophic lateral sclerosis can be modeled and probed with neurotoxic chemicals that induce similar patterns of pathology, such as axonal spheroids that represent focal accumulation of anterogradely transported neurofilaments (NFs). The aromatic gamma-diketone-like 1,2-diacetylbenzene (1,2-DAB), but not its 1,3-DAB isomer, reacts with epsilon-amino- or sulfyhydryl groups of (neuro)proteins, forms adducts, and causes NFs to accumulate at proximal sites of elongate motor axons. We exploit the protein-reactive properties of neurotoxic 1,2-DAB versus the nonprotein-reactive properties of non-neurotoxic 1,3-DAB to unveil proteomic changes associated with this type of pathology. We used two-dimensional differential in-gel electrophoresis (2D-DIGE), matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry to analyze the lumbosacral spinal cord proteome of adult Sprague-Dawley rats treated systemically with 20 mg/kg/day 1,2-DAB, equimolar dose of 1,3-DAB, or equivalent volume of vehicle (saline containing 2% acetone), 5 days a week, for 2 weeks. 1,2-DAB significantly altered the expression of protein disulfide isomerase, an enzyme involved in protein folding, and gelsolin, an actin-capping and -severing protein. Modifications of these two proteins have been incriminated in the pathogenesis of nerve fiber degeneration. Protein-reactive and neurotoxic 1,2-DAB appears to be excellent tool to dissect mechanisms of nerve fiber (axon) degeneration.

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