Targeting thioredoxin-1 with siRNA exacerbates oxidative stress injury after cerebral ischemia/reperfusion in rats

Li, L.; Zhu, Kunting; Liu, Y.; Wu, Xuemei; Wu, Jiayuan; Zhao, Yong; Zhao, Jintong

doi:10.1016/j.neuroscience.2014.10.066

Cited by 42 publications

(30 citation statements)

References 32 publications

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“…Moreover, Trx1 overexpression was shown to protect mice from neuronal apoptosis following mild focal ischemia [16]. In accordance with this evidence, the knock-down of Trx1 led to more pronounced neurological dysfunction, brain infarct size, brain edema, and overall peroxidation [17], as well as exacerbated apoptosis of neurons, behavioral deficits, and mortality [18]. Interestingly, the overexpression of the mitochondrial Trx2 attenuated ROS-induced TNF- α expression and subsequent NF- κ B activation and apoptosis [19].…”

Section: Introductionmentioning

confidence: 83%

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin‐2 Administration

Romero

Holubiec

Tornatore

et al. 2017

Oxidative Medicine and Cellular Longevity

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The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.

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Section: Introductionmentioning

confidence: 83%

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin‐2 Administration

Romero

Holubiec

Tornatore

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Previous studies have indicated that oxidative stress is involved in ischemic stroke, and attenuation of oxidative damage improves neurological outcome [32, 33]. MDA, a marker of lipid peroxidation, is one of the most commonly used indicators of oxidative stress [34].…”

Section: Discussionmentioning

confidence: 99%

α-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage

Maharjan

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Alpha-lipoic acid (α-LA) has been demonstrated to be protective against cerebral ischemia injury. Herein, we investigate the neuroprotective effect and underlying mechanisms of α-LA. Methods: In vivo study, α-LA was administered intravenously upon reperfusion of transient middle cerebral artery occlusion. Garcia score was used to evaluate neurologic recovery. Infarct volume was examined by TTC staining, and oxidative damage was evaluated by ELISA assay. In an in vitro study, neurons were pretreated with α-LA at different doses and then subjected to OGD. Lentiviral vectors were applied to knockdown nuclear factor-erythroid 2-related factor-2 (Nrf2) or heme oxygenase-1 (HO-1). Cell viability was measured using CCK8. Protein expression was evaluated using western blot, and immunofluorescence staining was assessed. Results: α-LA significantly reduced the infarct volume, brain edema, and oxidative damage and promoted neurologic recovery in rats. Pretreatment of α-LA caused an obvious increase in cell viability and a decrease in intracellular reactive oxygen species. Western blot analyses and immunofluorescence staining demonstrated a distinct increase in Nrf2 and HO-1 protein expression. Conversely, knockdown of Nrf2 or HO-1 resulted in the down-regulation of HO-1 protein and inhibited the neuroprotective effect of α-LA. Conclusion: α-LA treatment is neuroprotective and promotes functional recovery after ischemic stroke by attenuating oxidative damage, which is partially mediated by the Nrf2/HO-1 pathway.

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“…Oxygen tension regulates apoptosis in PC12 cells (Genetos et al 2010). Superoxide dismutase (SOD) reflects the level of ischemic tissue damage and plays a beneficial role in the response of the brain to oxidative stress (Li et al 2015). SOD is also a powerful antioxidant that catalyzes redox reactions by converting superoxide radicals into hydrogen peroxide and oxygen; thus, brain tissues are protected from further oxidative damage (Ciancarelli et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Sulfated Polysaccharide Isolated from the Sea Cucumber Stichopus japonicus Against PC12 Hypoxia/Reoxygenation Injury by Inhibition of the MAPK Signaling Pathway

Cui

Wang

et al. 2015

Cell Mol Neurobiol

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In this report, the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus can protect PC12 from Na2S2O4-induced hypoxia/reoxygenation (H/R) injury. SJP effectively improves cell viability and reduces extracellular LDH release in PC12 cells after H/R. Moreover, SJP significantly increases SOD activity but decreases MDA levels. Our experiments showed that SJP could significantly reduce cell apoptosis caused by H/R. Our current results demonstrate that SJP suppressed the activation of MAPKs, resulting in a significant decrease in Bax/Bcl-2 ratio, cleaved caspase-3/caspase-3, p53 phosphorylation, and cytochrome c release in a concentration-dependent manner. MAPK is closely related to H/R injury. SJP inhibited JNK1/2 and p38 MAPK activation but did not affect the increased ERK1/2 expression. These results suggested that JNK1/2 and p38 MAPK pathways could be involved in SJP-mediated attenuation of PC12 H/R injury. SJP prevented PC12 H/R injury in a dose-dependent manner, indicating that SJP may be developed as a candidate drug to prevent or treat cerebral ischemia-reperfusion injury.

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Targeting thioredoxin-1 with siRNA exacerbates oxidative stress injury after cerebral ischemia/reperfusion in rats

Cited by 42 publications

References 32 publications

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin‐2 Administration

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin‐2 Administration

α-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage

Sulfated Polysaccharide Isolated from the Sea Cucumber Stichopus japonicus Against PC12 Hypoxia/Reoxygenation Injury by Inhibition of the MAPK Signaling Pathway

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