Attenuation of neuronal degeneration in thioredoxin-1 overexpressing mice after mild focal ischemia

Zhou, Feng; Gomi, Masanori; Fujimoto, Motoaki; Hayase, Makoto; Marumo, Takeshi; Masutani, Hiroshi; Yodoi, Junji; Hashimoto, Nobuo; Nozaki, Kazuhiko; Takagi, Yasushi

doi:10.1016/j.brainres.2009.03.023

Cited by 49 publications

(31 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trx1 has also been shown to reduce and activate a number of transcription factors. Overexpression of Trx1 decreases the neuronal cell apoptosis induced by ischemia (Takagi et al, 1999; Zhou et al, 2009). …”

Section: Catalytic Antioxidant Defenses Against Neuronal Cell Deathmentioning

confidence: 99%

Antioxidant gene therapy against neuronal cell death

Navarro-Yepes

Zavala-Flores

Anandhan

et al. 2014

Pharmacology & Therapeutics

140

View full text Add to dashboard Cite

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy.

show abstract

Section: Catalytic Antioxidant Defenses Against Neuronal Cell Deathmentioning

confidence: 99%

Antioxidant gene therapy against neuronal cell death

Navarro-Yepes

Zavala-Flores

Anandhan

et al. 2014

Pharmacology & Therapeutics

140

View full text Add to dashboard Cite

show abstract

“…Transgenic mice overexpressing human Trx1 showed attenuated ischemic neuronal injury and significantly smaller infarct sizes when subjected to focal cerebral ischemia [15]. 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].…”

Section: Introductionmentioning

confidence: 99%

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

Romero

Holubiec

Tornatore

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

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.

show abstract

“…The effect of PX-12 on neuronal survival in focal ischemia is unknown. There are reports that overexpression or elevated expression of Trx-1 could be neuroprotective [28,29]. Further research is needed for the effects of Trx-1 on long-term neuronal survival.…”

Section: Discussionmentioning

confidence: 99%

Effects of the Thioredoxin-1 Inhibitor PX-12 on Blood-Brain Barrier Permeability in the Early Stage of Focal Cerebral Ischemia

Barsoum²,

Grayson³

et al. 2013

Pharmacology

View full text Add to dashboard Cite

Background/Aims: Since a thioredoxin-1 (Trx-1) inhibitor, 1-methylpropyl-2-imidazolyl disulfide (PX-12) which is an antitumor agent, significantly decreased vascular permeability in tumor xenografts within a few hours of treatment, we tested whether PX-12 would attenuate blood-brain barrier (BBB) disruption in the early stage of focal cerebral ischemia and whether its action could be affected by vascular endothelial growth factor (VEGF) which interacts with the Trx-1 system. Methods: In rats, 40 min after intravenous infusion of either 25 mg/kg of PX-12 (PX-12 group) or normal saline (control group), a middle cerebral artery (MCA) was occluded. In half of each group, VEGF (10^-10 mol/l) was applied topically in the ischemic cortex (IC). Ninety minutes after MCA occlusion, the transfer coefficient (K_i) of ¹⁴C-α-aminoisobutyric acid and the volume of ³H-dextran distribution were determined to measure the degree of BBB disruption. VEGF protein levels were determined using Western blot analysis. Results: MCA occlusion increased the K_i in the control (+196%) as well as in the PX-12-treated rats (+90%), but the K_i of the IC of the PX-12 group was lower (-42%) than that of the control rats. VEGF protein levels were decreased in both the IC (-9.5%) and the contralateral cortex (CC; -10.2%) with PX-12 treatment. In the VEGF-treated rats, PX-12 also attenuated (-41%) the K_i of the IC. The difference in the volume of dextran distribution between the IC and the CC became insignificant with PX-12 treatment with or without VEGF application. Conclusion: Our data demonstrated that PX-12 was effective in decreasing BBB disruption in the early stage of focal cerebral ischemia and that VEGF is not an important factor involved in the action of PX-12 on BBB permeability.

show abstract

Attenuation of neuronal degeneration in thioredoxin-1 overexpressing mice after mild focal ischemia

Cited by 49 publications

References 42 publications

Antioxidant gene therapy against neuronal cell death

Antioxidant gene therapy against neuronal cell death

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

Effects of the Thioredoxin-1 Inhibitor PX-12 on Blood-Brain Barrier Permeability in the Early Stage of Focal Cerebral Ischemia

Contact Info

Product

Resources

About