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Nanoparticles Exacerbate Both Ubiquitin and Heat Shock Protein Expressions in Spinal Cord Injury: Neuroprotective Effects of the Proteasome Inhibitor Carfilzomib and the Antioxidant Compound H-290/51

dc.contributor.authorSharma H.S.
dc.contributor.authorMuresanu D.F.
dc.contributor.authorLafuente J.V.
dc.contributor.authorSjöquist P.-O.
dc.contributor.authorPatnaik R.
dc.contributor.authorSharma A.
dc.date.accessioned2020-09-02T22:28:14Z
dc.date.available2020-09-02T22:28:14Z
dc.date.issued2015
dc.identifier10.1007/s12035-015-9297-9
dc.identifier.citation52, 2, 882-898
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6250
dc.descriptionIncreased levels of ubiquitin and heat shock protein (HSP) 72 kD are often seen in spinal cord injury (SCI). However, their roles in cell injury or survival are not well known. Thus, we have investigated the possible relationship between ubiquitin and HSP expressions in relation to cell injury in healthy animals, or following nanoparticle (NP) intoxication in SCI animals. A focal SCI was inflicted on the T10–11 segments over the right dorsal horn; animals were allowed to survive from 5 to 8 h after trauma. Separate groups of rats were exposed to SiO2, Ag, or Cu NPs for 7 days and subjected to SCI on the eighth day. A marked increase in ubiquitin or HSP immunoreactive cells occurred in the T9 to T12 segments 5 h after the injury, which further extended to the T4 and L5 after 8 h of survival. At this time, a marked increase in blood–spinal cord barrier (BSCB) permeability to Evans blue and radioiodine, accompanied by an intense edema formation, was observed. Changes were further exacerbated in NP-treated traumatized rats. The most marked expressions of ubiquitin and HSP in SCI were seen in rats treated with SiO2, followed by Ag, and Cu NPs. Treatment with H-290/51 (50 mg/kg p.o., 30 to 60 min after injury) or carfilzomib (1 mg/kg, i.v., 30 to 60 min after trauma) significantly reduced the ubiquitin or HSP expressions, as well as the BSCB breakdown, the edema formation, and the cell injury in the cord both 5 and 8 h after the injury, in normal animals. However, a double dose of H-290/51 (100 mg/kg) or carfilzomib (2 mg/kg) is needed to reduce cord pathology or ubiquitin and HSP expressions in traumatized animals treated with NPs. H-290/51 showed superior beneficial effects in reducing cord pathology in SCI than carfilzomib. These observations are the first to demonstrate that (i) NP-treated traumatized animals induce a widespread BSCB leakage, edema formation, and cord pathology as well as an overexpression of ubiquitin and HSP, (ii) high doses of antioxidant compounds or proteasome inhibitors are required for neuroprotection in the NP-exposed traumatized group, and (iii) ubiquitin and HSP expressions play a key role in neuronal injury in SCI, not reported earlier. © 2015, Springer Science+Business Media New York.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subjectBlood-spinal cord barrier
dc.subjectCarfilzomib
dc.subjectH-290/51
dc.subjectHeat shock protein
dc.subjectNanoparticle
dc.subjectSpinal cord injury
dc.subjectUbiquitin
dc.subjectantioxidant
dc.subjectcarfilzomib
dc.subjectcopper nanoparticle
dc.subjecth 290 51
dc.subjectheat shock protein
dc.subjectheat shock protein 72
dc.subjectnanoparticle
dc.subjectsilica nanoparticle
dc.subjectsilver nanoparticle
dc.subjectubiquitin
dc.subjectunclassified drug
dc.subjectantioxidant
dc.subjectcarfilzomib
dc.subjectcopper
dc.subjectH290-51
dc.subjectheat shock protein 72
dc.subjectindole derivative
dc.subjectnanoparticle
dc.subjectnerve protein
dc.subjectneuroprotective agent
dc.subjectoligopeptide
dc.subjectproteasome inhibitor
dc.subjectsilicon dioxide
dc.subjectsilver
dc.subjectubiquitin
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectblood spinal cord barrier
dc.subjectcontrolled study
dc.subjectdrug effect
dc.subjectedema
dc.subjectmale
dc.subjectnerve cell lesion
dc.subjectneuroprotection
dc.subjectnonhuman
dc.subjectpermeability barrier
dc.subjectprotein expression
dc.subjectrat
dc.subjectspinal cord dorsal horn
dc.subjectspinal cord injury
dc.subjectthoracic spinal cord
dc.subjectanimal
dc.subjectbiosynthesis
dc.subjectcomplication
dc.subjectedema
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectpathology
dc.subjectpreclinical study
dc.subjectspinal cord
dc.subjectSpinal Cord Injuries
dc.subjectthoracic vertebra
dc.subjectupregulation
dc.subjectWistar rat
dc.subjectAnimals
dc.subjectAntioxidants
dc.subjectCopper
dc.subjectDrug Evaluation, Preclinical
dc.subjectEdema
dc.subjectHSP72 Heat-Shock Proteins
dc.subjectIndoles
dc.subjectMale
dc.subjectNanoparticles
dc.subjectNerve Tissue Proteins
dc.subjectNeuroprotective Agents
dc.subjectOligopeptides
dc.subjectProteasome Inhibitors
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectSilicon Dioxide
dc.subjectSilver
dc.subjectSpinal Cord
dc.subjectSpinal Cord Injuries
dc.subjectThoracic Vertebrae
dc.subjectUbiquitin
dc.subjectUp-Regulation
dc.titleNanoparticles Exacerbate Both Ubiquitin and Heat Shock Protein Expressions in Spinal Cord Injury: Neuroprotective Effects of the Proteasome Inhibitor Carfilzomib and the Antioxidant Compound H-290/51
dc.typeArticle


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