Metal-catalyzed oxidation of bovine neurofilaments in vitro

Troncoso, Juan C.; Costello, Anthony C.; Kim, James H.; Johnson, Gail V.W.

doi:10.1016/0891-5849(94)00224-8

Cited by 34 publications

(23 citation statements)

References 42 publications

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“…Actin filaments, the major cellular target of HClO-, metaland 4-HNE-mediated oxidation [36,37], are also easily depolymerized upon carbonylation [38]. Neurofilament proteins, particularly NFM and NFH, are physiological substrates of 4-HNE and other RCOs [39], and carbonylation causes major changes in their secondary structure [40] leading to aggregation [41,42] and increased susceptibility to calpain-mediated proteolysis [43].…”

Section: Discussionmentioning

confidence: 99%

Lipid Peroxidation Scavengers Prevent the Carbonylation of Cytoskeletal Brain Proteins Induced by Glutathione Depletion

et al. 2007

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In this study, we investigated the possible link between lipid peroxidation (LPO) and the formation of protein carbonyls (PCOs) during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH depletor diethyl maleate (DEM) in the absence or presence of classical LPO scavengers: trolox, caffeic acid phenethyl ester (CAPE), and butylated hydroxytoluene (BHT). All three scavengers reduced DEM-induced lipid oxidation and protein carbonylation, suggesting that intermediates/products of the LPO pathway such as lipid hydroperoxides, 4-hydroxynonenal and/or malondialdehyde are involved in the process. Additional in vitro experiments revealed that, among these products, lipid hydroperoxides are most likely responsible for protein oxidation. Interestingly, BHT prevented the carbonylation of cytoskeletal proteins but not that of soluble proteins, suggesting the existence of different mechanisms of PCO formation during GSH depletion. In pull-down experiments, beta-actin and alpha/beta-tubulin were identified as major carbonylation targets during GSH depletion, although other cytoskeletal proteins such as neurofilament proteins and glial fibrillary acidic protein were also carbonylated. These findings may be important in the context of neurological disorders that exhibit decreased GSH levels and increased protein carbonylation such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

Lipid Peroxidation Scavengers Prevent the Carbonylation of Cytoskeletal Brain Proteins Induced by Glutathione Depletion

et al. 2007

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“…Recently, oxidative stress has been regarded as one of the most important factors contributing to the pathogenesis of several neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and stroke (Facchinetti et al 1998;Jenner and Olanow 1996;Lyras et al 1998;Munch et al 1998;Ramassamy et al 1999Ramassamy et al , 2000Smith et al 1996). Moreover, an increasing number of experimental observations strongly suggest that a dysfunction of NFs metabolism may result in the formation of NF-rich cytoplasmic inclusions (Cookson et al 1996;Montine et al 1995;Troncoso et al 1995;Tu et al 1997).…”

Section: Introductionmentioning

confidence: 99%

“…We used metal-catalyzed oxidation (MCO) employing the ascorbate-Fe +3 -O 2 system (Troncoso et al 1995) or oxidized catechols, namely dopamine (DA), 3,4dihydroxyphenylacetic acid (Dopac) and L-3,4-dihydroxyphenylalanine (L-dopa) (Montine et al 1995) on a substrate of phosphorylated or dephosphorylated NFs. We then demonstrated, by means of circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy, that NFs reorganize their primary and secondary structures in response to oxidative stress and as such may contribute to the formation of cytoplasmic inclusions in neurons.…”

Section: Introductionmentioning

confidence: 99%

Effect of oxidative stress on stability and structure of neurofilament proteins

Gélinas¹,

Chapados²,

Beauregard³

et al. 2000

Biochem. Cell Biol.

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Neurofilament proteins are highly phosphorylated molecules in the axonal compartment of the adult nervous system. We report the structural analysis of neurofilament proteins after oxidative damage. SDS-PAGE, immunoblotting, circular dichroism, and Fourier transform infrared spectroscopy were used to investigate the relative sensitivity of neurofilaments to oxidative stress and to identify changes in their molecular organization. An ascorbate-Fe+3-O2 buffer system as well as catechols were used to generate free radicals on a substrate of phosphorylated and dephosphorylated neurofilaments. By Fourier Transform Infrared spectroscopy and circular dichroism, we established that the neurofilament secondary structure is mainly composed of alpha-helices and that after free radical damage of the peptide backbone of neurofilaments, those helices are partly modified into beta-sheet and random coil structures. These characteristic reorganizations of the neurofilament structure after oxidative exposure suggest that free radical activity might play an important role in the biogenesis of the cytoplasmic inclusions found in several neurodegenerative diseases.

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“…It is evident that oxidative damage to neurofilaments can lead to cross-linking (Troncoso et al, 1995), which, in turn, could contribute to cytoskeletal abnormalities and impaired axonal transport. Both have been implicated in both SALS and FALS (Ince et al, 1996;Rouleau et al, 1996;Sasaki and Iwata, 1996;Shibata et al, 1996).…”

Section: Fig 3 Ohmentioning

confidence: 99%

Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

Se²,

La³

et al. 1997

Journal of Neurochemistry

713

406

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Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined markers of oxidative damage to protein, lipids, and DNA in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Protein carbonyl and nuclear DNA 8-hydroxy-2 '-deoxyguanosine (OH 8dG) levels were increased in SALS motor cortex but not in FALS patients. Malondialdehyde levels showed no significant changes. Immunohistochemical studies showed increased neuronal staining for hemeoxygenase-1, malondialdehydemodified protein, and OH8dG in both SALS and FALS spinal cord. These studies therefore provide further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both SALS and FALS.

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Metal-catalyzed oxidation of bovine neurofilaments in vitro

Cited by 34 publications

References 42 publications

Lipid Peroxidation Scavengers Prevent the Carbonylation of Cytoskeletal Brain Proteins Induced by Glutathione Depletion

Lipid Peroxidation Scavengers Prevent the Carbonylation of Cytoskeletal Brain Proteins Induced by Glutathione Depletion

Effect of oxidative stress on stability and structure of neurofilament proteins

Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

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