Hypothermia Affects Translocation of Numerous Cytoplasmic Proteins Following Global Cerebral Ischemia

Teilum, Maria; Krogh, Morten; Wieloch, Tadeusz; Mattiasson, Gustav

doi:10.1021/pr070057l

Cited by 7 publications

(4 citation statements)

References 75 publications

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“…Therefore, the preservation of a highly reduced intracellular environment may explain, at least in part, the neuronal protection afforded by hypothermia applied during an ischemic insult and reported previously for both in vivo and in vitro models (Lei et al, 1997;McManus et al, 2004). The maintenance of the GSH/GSSG ratio at values of ϳ130, without additional decrease, observed both at 37°C and 4°C after 15 min in the absence of blood flow, may be explained by decreased ROS production caused by tissue oxygen depletion (Teilum et al, 2007).…”

Section: Brain Tissue Redox State During Ischemiamentioning

confidence: 62%

Ischemia Enhances Activation by Ca²⁺and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Bull¹,

Finkelstein²,

Gálvez³

et al. 2008

J. Neurosci.

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Cerebral ischemia stimulates] changes. Endoplasmic reticulum vesicles were isolated from the cortex of rat brains incubated without blood flow for 5 min at 37°C (ischemic) or at 4°C (control). Ischemic brains displayed increased oxidative intracellular conditions, as evidenced by a lower ratio (ϳ130:1) of reduced/oxidized glutathione than controls (ϳ200:1). Single RyR channels from ischemic or control brains displayed the same three responses to Ca 2ϩ reported previously, characterized by low, moderate, or high maximal activity. Relative to controls, RyR channels from ischemic brains displayed with increased frequency the high activity response and with lower frequency the low activity response. Both control and ischemic cortical vesicles contained the RyR2 and RyR3 isoforms in a 3:1 proportion, with undetectable amounts of RyR1. Ischemia reduced [ 3 H]ryanodine binding and total RyR protein content by 35%, and increased at least twofold endogenous RyR2 S-nitrosylation and S-glutathionylation without affecting the corresponding RyR3 endogenous levels. In vitro RyR S-glutathionylation but not S-nitrosylation favored the emergence of high activity channels. We propose that ischemia, by enhancing RyR2 S-glutathionylation, allows RyR2 to sustain CICR; the resulting amplification of Ca 2ϩ entry signals may contribute to cortical neuronal death.

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Section: Brain Tissue Redox State During Ischemiamentioning

confidence: 62%

Ischemia Enhances Activation by Ca²⁺and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Bull¹,

Finkelstein²,

Gálvez³

et al. 2008

J. Neurosci.

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“…In cerebral ischemia, this approach has been used to uncover key molecular events using a cerebral ischemic model. [24][25][26] However, there have been no studies of pain-associated regions such as the spinal cord or sciatic nerve using cerebral ischemic animal models.…”

mentioning

confidence: 99%

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

Harada

Matsuura

Takano

et al. 2016

Biological & Pharmaceutical Bulletin

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Central post-stroke pain (CPSP) is one of the complications of cerebral ischemia and neuropathic pain syndrome. At present, there are few studies of pain in regions such as the spinal cord or sciatic nerve in cerebral ischemic animal models. To identify proteomic changes in the spinal cord and sciatic nerve in global cerebral ischemic model mice, in the present study we performed an investigation using proteomic methods. In a comparison between the intensity of protein spots obtained from a sham and that from a bilateral carotid artery occulusion (BCAO) in spinal cord and sciatic nerve, the levels of 10 (spinal cord) and 7 (sciatic nerve) protein spots were altered. The protein levels in the spinal cord were significantly increased in N G ,N Gdimethylarginine dimethylaminohydrolase 1 (DDAH1), 6-phosphogluconolactonase isoform 1, and precursor apoprotein A-I and decreased in dihydropyrimidinase-related protein 2 (CRMP-2), enolase 1B, rab guanosine 5′-diphosphate (GDP) dissociation inhibitor beta, septin-2 isoform a, isocitrate dehydrogenase subunit alpha, cytosolic malate dehydrogenase, and adenosine triphosphate synthase. The protein levels in the sciatic nerve were significantly increased in a mimecan precursor, myosin light chain 1/3, and myosin regulatory light chain 2 (MLC2), and decreased in dihydropyrimidinase-related protein 3 (CRMP-4), protein disulfideisomerase A3, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, and B-type creatine kinase. In addition, CRMP-2 and CRMP-4 protein levels were decreased, and DDAH1 and MLC2 protein levels were increased on day 1 after BCAO using Western blotting. These results suggested that changes in these proteins may be involved in the regulation of CPSP.Key words global ischemia; pain; spinal cord; sciatic nerve; proteome Cerebral stroke remains one of the leading causes of death and disability worldwide.1) Recent insights into the basic mechanism involved in ischemic stroke indicate that endothelial dysfunctions along with oxidative stress and neuroinflammation are key elements in the occurrence and development of ischemic brain damage that results in cell damage and death.2,3) Many clinical symptoms can manifest after strokes, including motor deficits, cognitive dysfunction, language problems, emotional disturbances, social maladjustment, somatosensory dysfunction, and central pain. 4,5) Cerebral stroke occasionally induces central post-stroke pain (CPSP) that manifests as burning pain, throbbing pain, aching pain, slashing pain, allodynia, and hyperalgesia, either continuously or intermittently on the affected side.6,7) CPSP is known to be one of the neuropathic pain.8) Neuropathic pain is defined as "pain initiated or caused by a primary lesion or dysfunction of the nervous system." It can be a debilitating and difficult condition to treat and is often resistant to simple analgesics, requiring additional analgesic treatment. 9)Some hypotheses of the pathophysiological mechanisms of somatosensory dysfunction have been proposed to explain CPSP symptoms, such as the ...

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“…DRP2 protein is a member of the collapsin response mediator protein (CRMP)/DRP cytosolic phosphoproteins family [ 30 ], mostly expressed in brain and involved in axonal growth direction [ 43 ]. DRP2 has been described in diverse global and focal ischemia models, identifying different phosphorylated forms, or isoforms of DRP2 with different response to ischemia [ 30 , 32 , 35 , 60 , 61 , 62 , 63 ]. Cuadrado et al [ 31 ] described different isoforms of DRP2 in human patients with cerebral infarct.…”

Section: Discussionmentioning

confidence: 99%

Differential Association of 4E-BP2-Interacting Proteins Is Related to Selective Delayed Neuronal Death after Ischemia

Martínez‐Alonso

Guerra-Pérez

Escobar-Peso

et al. 2021

IJMS

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Cerebral ischemia induces an inhibition of protein synthesis and causes cell death and neuronal deficits. These deleterious effects do not occur in resilient areas of the brain, where protein synthesis is restored. In cellular stress conditions, as brain ischemia, translational repressors named eukaryotic initiation factor (eIF) 4E-binding proteins (4E-BPs) specifically bind to eIF4E and are critical in the translational control. We previously described that 4E-BP2 protein, highly expressed in brain, can be a molecular target for the control of cell death or survival in the reperfusion after ischemia in an animal model of transient cerebral ischemia. Since these previous studies showed that phosphorylation would not be the regulation that controls the binding of 4E-BP2 to eIF4E under ischemic stress, we decided to investigate the differential detection of 4E-BP2-interacting proteins in two brain regions with different vulnerability to ischemia-reperfusion (IR) in this animal model, to discover new potential 4E-BP2 modulators and biomarkers of cerebral ischemia. For this purpose, 4E-BP2 immunoprecipitates from the resistant cortical region and the vulnerable hippocampal cornu ammonis 1 (CA1) region were analyzed by two-dimensional (2-D) fluorescence difference in gel electrophoresis (DIGE), and after a biological variation analysis, 4E-BP2-interacting proteins were identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Interestingly, among the 4E-BP2-interacting proteins identified, heat shock 70 kDa protein-8 (HSC70), dihydropyrimidinase-related protein-2 (DRP2), enolase-1, ubiquitin carboxyl-terminal hydrolase isozyme-L1 (UCHL1), adenylate kinase isoenzyme-1 (ADK1), nucleoside diphosphate kinase-A (NDKA), and Rho GDP-dissociation inhibitor-1 (Rho-GDI), were of notable interest, showing significant differences in their association with 4E-BP2 between resistant and vulnerable regions to ischemic stress. Our data contributes to the first characterization of the 4E-BP2 interactome, increasing the knowledge in the molecular basis of the protection and vulnerability of the ischemic regions and opens the way to detect new biomarkers and therapeutic targets for diagnosis and treatment of cerebral ischemia.

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Hypothermia Affects Translocation of Numerous Cytoplasmic Proteins Following Global Cerebral Ischemia

Cited by 7 publications

References 75 publications

Ischemia Enhances Activation by Ca²⁺and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Ischemia Enhances Activation by Ca²⁺and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

Differential Association of 4E-BP2-Interacting Proteins Is Related to Selective Delayed Neuronal Death after Ischemia

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Hypothermia Affects Translocation of Numerous Cytoplasmic Proteins Following Global Cerebral Ischemia

Cited by 7 publications

References 75 publications

Ischemia Enhances Activation by Ca2+and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Ischemia Enhances Activation by Ca2+and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

Differential Association of 4E-BP2-Interacting Proteins Is Related to Selective Delayed Neuronal Death after Ischemia

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Product

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Ischemia Enhances Activation by Ca²⁺and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex

Ischemia Enhances Activation by Ca²⁺and Redox Modification of Ryanodine Receptor Channels from Rat Brain Cortex