The role of poly(ADP-ribose) metabolism in response to active oxygen cytotoxicity

Lautier, Dominique; Hoflack, Jean-Christophe; Kirkland, James B.; Poirier, D.; Poirier, Guy G.

doi:10.1016/0167-4889(94)90243-7

Cited by 18 publications

(11 citation statements)

References 21 publications

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“…of six different blood samples and is expressed as percentage of AMP-deaminase activity (control hemolysates ϭ 100% of activity). metabolism, oxidative stress might certainly represent a negative factor whose relevance, unlike that of other tissues (5,17) and cell types (18,19) has not been fully evaluated. Previous investigation, using iron ascorbate as a ROS-generating system, apparently showed a poor capacity of oxidative stress to alter enzymes and metabolites of human red blood cell energy metabolism (12).…”

Section: Table IV Effect Of P I On the Amp-deaminase Activity Of Humamentioning

confidence: 99%

Oxidative Stress Induces Impairment of Human Erythrocyte Energy Metabolism through the Oxygen Radical-mediated Direct Activation of AMP-deaminase

Tavazzi

Amorini

Fazzina

et al. 2001

Journal of Biological Chemistry

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The effect of oxidative stress on human red blood cell AMP-deaminase activity was studied by incubating either fresh erythrocytes or hemolysates with H 2 O 2 (0.5, 1, 2, 4, 6, 8, and 10 mM) or NaNO 2 (1, 5, 10, 20, and 50 mM), for 15 min at 37°C. AMP-deaminase tremendously increased by increasing H 2 O 2 or NaNO 2 at up to 4 and 20 mM, respectively (maximal effect for both oxidants was 9.5 and 6.5 times higher enzymatic activity than control erythrocytes or hemolysates, respectively). The incubation of hemolysates with iodoacetate (5-100 mM), N-ethylmaleimide (0.1-10 mM), or p-hydroxymercuribenzoate (0.1-5 mM) mimicked the effect of oxidative stress on AMP-deaminase, indicating that sulfhydryl group modification is involved in the enzyme activation. Reactive oxygen species (ROS) 1 are dangerous molecules generated physiologically and pathologically from various intracellular and extracellular sources (1). Several ROS-induced irreversible modifications of biologically fundamental macromolecules have been described, including oxidation of protein -SH groups (2), oxidation of purine nucleotides of nucleic acids (3), and initiation of lipid peroxidation reaction chain (4, 5). Due to their very high ferrous iron concentration, human erythrocytes might be exposed to risks of increased oxidative stress, mainly through the formation of ferrylhemoglobin (6) and, in part, through the Fenton reaction of hydrogen peroxide with Fe 2ϩ of hemoglobin, which generates the powerful oxidant hydroxyl radical (7). Although provided with efficient enzymatic systems for H 2 O 2 removal (catalase, glutathione peroxidase), several ROS-mediated erythrocyte damages have been reported to occur in different in vitro experimental conditions, including challenge with hydrogen peroxide (8, 9), incubation with redox-cycling drugs (10), and during the aging process (11). Nevertheless, data available in the literature give very little information on alteration of erythrocyte energy metabolism (in terms either of metabolites or of enzymatic activities) following oxidative stress, except for results reporting only modest effects of iron-ascorbate (as a ROS-generating system) on hexokinase (12), thus suggesting that enzymes involved in red blood cell energy production are scarcely affected by oxidative stress.Very recently, we have shown, on the contrary, that oxidative stress, induced by increasing the addition of H 2 O 2 concentrations to intact red blood cells, provoked a progressive ATP depletion, which was unexpectedly paralleled by a marked IMP (but neither AMP nor ADP) increase. Such a phenomenon was very probably linked to AMP-deaminase 2 activation (13). This enzyme plays a critical role in energy metabolism, catalyzing the deamination of AMP into IMP in the purine nucleotide cycle, and it is present in mammals in three different isoforms.

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Section: Table IV Effect Of P I On the Amp-deaminase Activity Of Humamentioning

confidence: 99%

Oxidative Stress Induces Impairment of Human Erythrocyte Energy Metabolism through the Oxygen Radical-mediated Direct Activation of AMP-deaminase

Tavazzi

Amorini

Fazzina

et al. 2001

Journal of Biological Chemistry

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“…To date, possible mechanisms for this phenomenon are the hydroxyl radical-induced hydrolysis of the N-glycosidic bond of the reduced forms of NAD and NADP and the activation of the enzyme NAD-glycohydrolase. 43 Both mechanisms cause the hydrolysis of nicotinic coenzymes and give rise to the same end products-ADP-ribose(P) and nicotinamide. Independent of the predominant mechanism, the final result is certainly deleterious for the correct functioning of cell metabolism.…”

Section: Energy Metabolism and Naa Synthesismentioning

confidence: 99%

Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications

Signoretti

Vagnozzi

Tavazzi

et al. 2010

FOC

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Although numerous studies have been carried out to investigate the pathophysiology of mild traumatic brain injury (mTBI), there are still no standard criteria for the diagnosis and treatment of this peculiar condition. The dominant theory that diffuse axonal injury is the main neuropathological process behind mTBI is being revealed as weak at best or inconclusive, given the current literature and the fact that neuronal injury inherent to mTBI improves, with few lasting clinical sequelae in the vast majority of patients. Clinical and experimental evidence suggests that such a course, rather than being due to cell death, is based on temporal neuronal dysfunction, the inevitable consequence of complex biochemical and neurochemical cascade mechanisms directly and immediately triggered by the traumatic insult. This report is an attempt to summarize data from a long series of experiments conducted in the authors' laboratories and published during the past 12 years, together with an extensive analysis of the available literature, focused on understanding the biochemical damage produced by an mTBI. The overall clinical implications, as well as the metabolic nature of the post-mTBI brain vulnerability, are discussed. Finally, the application of proton MR spectroscopy as a possible tool to monitor the full recovery of brain metabolic functions is emphasized.

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“…(EC 2.4.2.30) catalyzes the transfer of the ADP-ribose moiety from its substrate NAD ϩ , to a limited number of proteins involved in chromatin architecture, DNA repair, or in DNA metabolism including PARP itself (1)(2)(3)(4). Recently, the generation of PARP-deficient mice by homologous recombination (5,6) has clearly demonstrated the involvement of PARP in the maintenance of the genomic integrity due to its role during base excision repair (7)(8)(9)).…”

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confidence: 99%

PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase

Amé¹,

Rolli²,

Schreiber³

et al. 1999

Journal of Biological Chemistry

667

334

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Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins in response to DNA damage that activates the base excision repair machinery. Poly-(ADP-ribose) polymerase which we will now call PARP-1, has been the only known enzyme of this type for over 30 years. Here, we describe a cDNA encoding a 62-kDa protein that shares considerable homology with the catalytic domain of PARP-1 and also contains a basic DNA-binding domain. We propose to call this enzyme poly(ADP-ribose) polymerase 2 (PARP-2). The PARP-2 gene maps to chromosome 14C1 and 14q11.2 in mouse and human, respectively. Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vitro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-dependent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleus in vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.In response to DNA-strand breaks introduced either directly by ionizing radiation or indirectly following enzymatic incision at a DNA lesion, the immediate poly(ADP-ribosylation) of nuclear proteins converts the DNA ends into intracellular signals that modulate DNA repair and cell survival programs. At the sites of DNA breakage, poly(ADP-ribose) polymerase (PARP) 1 (EC 2.4.2.30) catalyzes the transfer of the ADP-ribose moiety from its substrate NAD ϩ , to a limited number of proteins involved in chromatin architecture, DNA repair, or in DNA metabolism including PARP itself (1-4). Recently, the generation of PARP-deficient mice by homologous recombination (5, 6) has clearly demonstrated the involvement of PARP in the maintenance of the genomic integrity due to its role during base excision repair (7-9). An substantial delay in DNA strandbreak repair was observed following treatment of PARP-deficient cells with monofunctional alkylating agents (10). This severe DNA repair defect appears to be the primary cause for the observed cytotoxicity of N-methyl-N-nitrosourea, methylmethanesulfonate (MMS), or ␥-rays leading to cell death occurring after a G 2 /M block (10).It was assumed for many years that PARP activity was associated with a single protein displaying unique DNA damage detection and signaling properties. This assumption was challenged by the recent discovery in Arabidopsis thaliana of a gene coding for a PARP-related polypeptide of a calculated molecular mass of 72 kDa (11). It then became evident that two structurally different PARP proteins, both possessing DNA-dependent poly(ADP-ribose) activities, were present in both A. thaliana as well as in maize (12)(13)(14). 2 Furthermore, it has been reported recently that mouse embryonic fibroblasts derived from PARP knockout are capable of synthesizing ADP-ribose polymers in response to DNA damage (15), suggesting that in mammals, like in plants, at least one additional member of the PARP family may exist in addition to the classical zinc finger containing PAR...

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The role of poly(ADP-ribose) metabolism in response to active oxygen cytotoxicity

Cited by 18 publications

References 21 publications

Oxidative Stress Induces Impairment of Human Erythrocyte Energy Metabolism through the Oxygen Radical-mediated Direct Activation of AMP-deaminase

Oxidative Stress Induces Impairment of Human Erythrocyte Energy Metabolism through the Oxygen Radical-mediated Direct Activation of AMP-deaminase

Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications

PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase

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