Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients

Nikolić‐Kokić, Aleksandra; Stević, Zorica; Blagojević, Duško; Davidović, Biljana; Jones, David R.; Spasić, Mihajlo

doi:10.1515/cclm.2006.111

Cited by 47 publications

(34 citation statements)

References 31 publications

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“…In fact, a recent series of studies suggest the possibility of systemic involvement in sALS [27]. In ALS patients, cultured monocytes have increased inflammatory cytokine production [28], cutaneous collagen fibers are abnormal [29], systemic glutamate metabolism is impaired [30], the antioxidative defense system of erythrocytes is reduced [31], patients are in a hypermetabolic state due to abnormal skeletal muscle metabolism [32], and muscle mitochondria are not only structurally abnormal [33,34], but have primary abnormalities known to cause an ALS-like syndrome [35]. A major source of 'systemic' oxidative stress is clearly generated in skeletal muscle, which constitutes 40 to 45% of body mass [36].…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress biomarkers in sporadic ALS

Mitsumoto

Santella

Liu

et al. 2008

Amyotrophic Lateral Sclerosis

152

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Objective-To investigate oxidative stress biomarkers in a cross-sectional pilot study of 50 participants with sporadic ALS (sALS) compared to 46 control subjects.Methods-We measured urinary 8-oxodeoxyguanosine (8-oxodG), urinary 15-F 2t -isoprostane (IsoP), and plasma protein carbonyl by ELISA methods. We also determined if ELISA measurement of 8-oxodG could be validated against measures from high pressure liquid chromatography coupled with electrochemical detection, the current standard method.Results-8-oxodG and IsoP levels adjusted for creatinine were significantly elevated in sALS participants. These differences persisted after age and gender were controlled in regression analyses. These markers are highly and positively correlated with each other. 8-oxodG measured by the two techniques from the same urine sample were positively correlated (P < .0001). Protein carbonyl was not different between sALS participants and controls.Conclusion-Using ELISA we confirmed that certain oxidative stress biomarkers were elevated in sALS participants. ELISA may be reliable and thus useful in epidemiology studies requiring

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Section: Discussionmentioning

confidence: 99%

Oxidative stress biomarkers in sporadic ALS

Mitsumoto

Santella

Liu

et al. 2008

Amyotrophic Lateral Sclerosis

152

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“…The ADS in human erythrocytes with preserved homeostasis finely retunes its composition according to plasma oxidative demands. An increase in the level of a specific plasma lipid component may potentiate mem brane lipid peroxidation in erythrocytes and decrease intraerythrocyte production of O 2 .-, which could result in a negative correlation between SOD and GSH-Px activities found in some experiments (6)(7)(8)(9). The discovery of the haemoglobin-cholesterol (Hb-Ch) complex implies the way in which cholesterol may influence the organisation of ADS in erythrocytes (7).…”

Section: Introductionmentioning

confidence: 99%

“…Non-specific inter actions of ROS with different classes of intracellular molecules induce oxidative damage leading to the impairment of cellular homeostasis. As accurate detection of in vivo ROS concentrations is still problematic, changes in the ADS may serve as a good indicator of processes within the organism, as it responds to ROS production, changes of the environment (as low environmental temperature) (11) and pathological conditions (9). It should be stressed that the ADS is species-and tissue-specific (12) and that antioxidative enzymes in erythrocytes and the do minant source of ROS in erythrocytes are in many aspects quite different in comparison with extracellular fluids and other tissues.…”

Section: Introductionmentioning

confidence: 99%

Complexity of free radical Metabolism in human Erythrocytes

Nikolić‐Kokić¹,

Blagojević²,

Spasić³

2010

Journal of Medical Biochemistry

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Kratak sadr`aj: Produkcija slobodnih radikala u eritrocitima uglavnom se odnosi na nastajanje superoksid anjon radikala (O 2 .-) putem autooksidacije oksihemoglobina u methemoglobin. Ljudski eritrociti izlo`eni su prooksidacionom delovanju vodonik-peroksida nastalog dismutacijom O 2 .-ili iz cirkulacije, kao i azot oksidu (NO) iz cirkulacije. Od di rektnih reakcija slobodnih radikala, reakcija O 2 .-i NO uz nastajanje peroksinitrita je reakcija sa primarno {tetnim posledicama po eritrocite. U eritrocitima se nalaze enzimi za{tite od oksidacionih o{te}enja, kao {to su superoksid dismu taza (SOD, EC 1.15.1.1), katalaza (CAT, EC 1.11.1.6), glutation peroksidaza (GSHPx, EC 1.11.1.9) i glutation reduktaza (GR, EC 1.6.4.2) kao i komponente male mo lekulske mase (glutation, vitamini E i C). Njihovim sadej stvom se kanali{u reakcije slobodnih radikala tako da di rektna o{te -}enja biomakromolekula budu {to manja. Me|u tim, kako nema de novo sinteze enzima u maturiranim eri trocitima, kapacitet ovih sistema je ograni~en, jer slobo d noradikalske vrste i direktno inhibiraju neke od enzima. Promene na enzimima i njihova inhibicija slobodnim radi kalima uti~u na kapacitet za{tite od oksidacionih o{te}enja i relativni udeo pojedinih komponenti u ukupnom antioksi da tivnom poten cijalu. To se mo`e pratiti i preko promena aktiv nosti pojedina~nih komponenti, ali i me |u sobnih odnosa izme|u komponenti antioksidativne odbrane diskrimina cio nim sta ti sti ~kim metodama, koje ukazuju na sveukupnost i kompleksnost odnosa antioksida tivnih kompo nenti u eritro citima i njihov sistemski zna~aj.

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“…Evidence for oxidative damage to proteins and lipids has been detected in serum, fibroblasts, and the central nervous system (CNS) of ALS patients as well as various organs in the G93A mutant SOD1 transgenic murine model of ALS (13)(14)(15)(16)(17)(18)(19)(20). A central regulator of cellular responses to oxidative stress is the NRF2 (NF-E2-related factor 2)/KEAP1 (Kelch-like ECH-associated protein 1) pathway.…”

mentioning

confidence: 99%

RBM45 Modulates the Antioxidant Response in Amyotrophic Lateral Sclerosis through Interactions with KEAP1

Bakkar

Kousari

Kovalik

et al. 2015

Molecular and Cellular Biology

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of motor neurons. Various factors contribute to the disease, including RNA binding protein dysregulation and oxidative stress, but their exact role in pathogenic mechanisms remains unclear. We have recently linked another RNA binding protein, RBM45, to ALS via increased levels of protein in the cerebrospinal fluid of ALS patients and its localization to cytoplasmic inclusions in ALS motor neurons. Here we show RBM45 nuclear exit in ALS spinal cord motor neurons compared to controls, a phenotype recapitulated in vitro in motor neurons treated with oxidative stressors. We find that RBM45 binds and stabilizes KEAP1, the inhibitor of the antioxidant response transcription factor NRF2. ALS lumbar spinal cord lysates similarly show increased cytoplasmic binding of KEAP1 and RBM45. Binding of RBM45 to KEAP1 impedes the protective antioxidant response, thus contributing to oxidative stress-induced cellular toxicity. Our findings thus describe a novel link between a mislocalized RNA binding protein implicated in ALS (RBM45) and dysregulation of the neuroprotective antioxidant response seen in the disease.A myotrophic lateral sclerosis (ALS) is a fatal idiopathic adultonset neurodegenerative disease characterized by a loss of motor neurons in the brain, brain stem, and spinal cord, with consequent atrophy of associated muscles (1, 2). Incidence rates are 1 to 3 cases per 100,000 individuals per year. Pathogenic mechanisms underlying the disease are not fully understood. Approximately 5 to 10% of all ALS cases are familial (3), with the remaining cases being termed sporadic, contributing to the clinical heterogeneity within the patient population. Nevertheless, typical hallmarks of ALS include neuronal atrophy, mitochondrial dysfunction, excitotoxicity, oxidative stress, and ubiquitinated cellular inclusions (4, 5). A growing number of genes with diverse functions have been implicated in the disease etiology. Mutations in a number of RNA binding proteins have been linked to ALS, including TAR DNA binding protein 43 (TDP-43) and Fused in Sarcoma (FUS) (6). Mutations in these genes result in reduced levels in the nucleus and their accumulation in cytoplasmic ubiquitin-positive inclusions (7). Both TDP-43 and FUS possess prion-like domains and relocate to cytoplasmic stress granules under stress conditions, suggesting potential pathology commonalities (8). Genetic alterations in these and other RNA binding proteins link RNA metabolism to the pathobiology of ALS.Recently, we linked another RNA binding protein, RBM45, to ALS using a proteomic screen of cerebrospinal fluid (CSF) from ALS and control subjects (9). RBM45, also known as Drb1, was first identified as a novel RNA binding protein that functions in neural development (10). RBM45 possesses three RNA recognition motifs (RRMs) as well as a C-terminal nuclear localization sequence (10). By using a large liquid chromatography-tandem mass spectrometry (LC-MS/MS) unbia...

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Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients

Cited by 47 publications

References 31 publications

Oxidative stress biomarkers in sporadic ALS

Oxidative stress biomarkers in sporadic ALS

Complexity of free radical Metabolism in human Erythrocytes

RBM45 Modulates the Antioxidant Response in Amyotrophic Lateral Sclerosis through Interactions with KEAP1

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