Reduction of tyrosine nitration after Nω-nitro-l-arginine-methylester treatment of mice with traumatic brain injury

Mésenge, Christian; Charriaut‐Marlangue, Christiane; Verrecchia, C.; Allix, Monique; Boulu, R; Plotkine, Michel

doi:10.1016/s0014-2999(98)00432-4

Cited by 71 publications

(48 citation statements)

References 25 publications

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“…Indeed, many neurotoxic signaling mechanisms have been implicated after TBI. Caspases (Yakovlev et al, 1997;Clark et al, 1999Clark et al, , 2000Beer et al, 2000Beer et al, , 2001Knoblach et al, 2002), calpains (Pike et al, 1998Buki et al, 1999;Knoblach et al, 2004), PARP-1 (LaPlaca et al, 2001;Besson et al, 2003;Hortobagyi et al, 2003), reactive nitrogen species (Mesenge et al, 1998;Hall et al, 2004), and reactive oxygen species (Marklund et al, 2001a,b) have all been suggested to play key roles in TBI. In addition, it is recognized that cross talk may exist between signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Caspase-Mediated Apoptosis by Peroxynitrite in Traumatic Brain Injury

Lau¹,

Arundine²,

Sun³

et al. 2006

J. Neurosci.

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In traumatic brain injury (TBI), neurons surviving the primary insult may succumb through poorly understood secondary mechanisms. In vitro, cortical neurons exposed to stretch injury exhibited enhanced vulnerability to NMDA, apoptotic-like DNA fragmentation, peroxynitrite (PN) formation, and cytoplasmic cytochrome c accumulation. Surprisingly, caspase-3 activity was undetectable by both immunoblotting and fluorogenic activity assays. Therefore, we hypothesized that PN directly inhibits caspases in these neurons. Consistent with this, stretch injury in cultured neurons elicited tyrosine nitration of procaspase-3, but not caspase-9 or Apaf-1, suggesting a direct interaction of PN with caspase-3. In an ex vivo system, PN inhibited the activity of caspase-3, and this inhibition was reversible with the addition of the sulfhydryl reducing agent dithiothreitol, indicating that PN inhibits caspases by cysteinyl oxidation. Moreover, in cultures, the PN donor 3-morpholinosydnonimine (SIN-1) blocked staurosporine-induced caspase-3 activation and its downstream effects including PARP-1 [poly-(ADP-ribose) polymerase-1] cleavage and phosphotidylserine inversion, suggesting that peroxynitrite can inhibit caspase-3-mediated apoptosis. To examine these mechanisms in vivo, rats were exposed to a lateral fluid percussion injury (FPI). FPI caused increased neuronal protein nitration that colocalized with TUNEL staining, indicating that PN was associated with neurodegeneration. Caspase-3 activity was inhibited in brain lysates harvested after FPI and was restored by adding dithiothreitol. Our data show that caspase-mediated apoptosis is inhibited in neurons subjected to stretch in vitro and to TBI in vivo, mostly because of cysteinyl oxidation of caspase-3 by PN. However, this is insufficient to prevent cell death, indicating that the TBI therapy may, at a minimum, require a combination of both anti-apoptotic and anti-oxidant strategies.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Caspase-Mediated Apoptosis by Peroxynitrite in Traumatic Brain Injury

Lau¹,

Arundine²,

Sun³

et al. 2006

J. Neurosci.

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“…Both penicillamine (Hall et al, 1999) and tempol (Beit-Yannai et al, 1996) have been reported to improve neurological recovery in rodent TBI models. Moreover, administration of the NOS inhibitors nitro-arginine methyl ester and 7-nitroindazole have been shown to improve neurological recovery in head-injured mice (Mesenge et al, 1996) together with a reduction in brain 3NT levels (Mesenge et al, 1998).…”

Section: Sources Of Peroxynitritementioning

confidence: 99%

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Deng

Thompson

Gao

et al. 2007

Experimental Neurology

133

171

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We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time-course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 hrs, 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca ++ -activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein α-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 hrs before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. α-Spectrin breakdown products, which was used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 hrs post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 hrs post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca ++ homeostatic mechanisms which causes a massive Ca ++ overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.

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“…Moreover, free radical production is triggered by TBI [184][185][186][187][188][189] and SCI [182,183,[190][191][192]. The involvement of oxidative stress and NO have been well established in both brain [193][194][195][196][197][198][199][200][201][202][203][204] and spinal cord trauma [171,178,181,[205][206][207][208][209][210][211][212][213][214][215][216]. As superoxide anions are produced after TBI [186] and SCI [217], the cytotoxic oxidant peroxynitrite is formed.…”

Section: Upstream Processes Involved In Parp Activation In Neurotraumamentioning

confidence: 99%

“…As superoxide anions are produced after TBI [186] and SCI [217], the cytotoxic oxidant peroxynitrite is formed. Indeed, it has been demonstrated in the traumatic spinal cord [177,182,183,217,218] and brain tissue [145,198,219,220]. Additionally, peroxynitrite is involved in neuronal cell death and neurological deficits following TBI [221,222] and SCI [223].…”

Section: Upstream Processes Involved In Parp Activation In Neurotraumamentioning

confidence: 99%

Poly (ADP-Ribose) Polymerase Inhibitors as Potential Therapeutic Agents in Stroke and Neurotrauma

2005

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Poly (ADP-ribose) polymerase-1 (PARP-1) is a DNA-binding protein that is primarily activated by nicks in the DNA molecule. It regulates the activity of various enzymes - including itself- that are involved in the control of DNA metabolism. Upon binding to DNA breaks, activated PARP cleaves NAD+ into nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor proteins including histones, transcription factors and PARP itself. Poly(ADP-ribosylation) contributes to DNA repair and to the maintenance of genomic stability. Evidence obtained with pharmacological PARP inhibitors of various structural classes, as well as animals lacking the PARP-1 enzyme indicate that PARP plays an important role in cerebral ischemia/reperfusion, stroke and neurotrauma. Overactivation of PARP consumes NAD+ and ATP culminating in cell dysfunction and necrosis. PARP activation can also act as a signal that initiates cell death programs, for instance through AIF (apoptosis inducing factor) translocation. PARP has also been shown to associate with and regulate the function of several transcription factors. Of special interest is the enhancement by PARP of NF-kappaB-mediated transcription, which plays a central role in the expression of inflammatory cytokines, chemokines, adhesion molecules and inflammatory mediators. Via this mechanism, PARP is involved in the up-regulation of numerous pro-inflammatory genes that play a pathogenetic role in the later stage of stroke and neurotrauma. Here we review the roles of PARP in DNA damage signaling and cell death, and summarize the pathogenetic role of PARP in stroke and neurotrauma.

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Reduction of tyrosine nitration after Nω-nitro-l-arginine-methylester treatment of mice with traumatic brain injury

Cited by 71 publications

References 25 publications

Inhibition of Caspase-Mediated Apoptosis by Peroxynitrite in Traumatic Brain Injury

Inhibition of Caspase-Mediated Apoptosis by Peroxynitrite in Traumatic Brain Injury

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Poly (ADP-Ribose) Polymerase Inhibitors as Potential Therapeutic Agents in Stroke and Neurotrauma

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