Oxidative Stress: Emerging Mitochondrial and Cellular Themes and Variations in Neuronal Injury

Higgins, Gavin C; Beart, Philip M; Shin, Yea Seul; Chen, Minghui Jessica; Cheung, Nam Sang; Nagley, Phillip

doi:10.3233/jad-2010-100321

Cited by 134 publications

(102 citation statements)

References 162 publications

(196 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among these two pathways, cell death induced by changes of oxidative phosphorylation in the mitochondria is a critical factor for neuron loss in AD and PD (18,27). In G114V gCJD, distinct impediment of oxidation phosphorylation is also observed.…”

Section: Discussionmentioning

confidence: 99%

Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease

Tian

Chen

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Familial or genetic Creutzfeldt-Jakob disease (fCJD or gCJD) is an inherent human prion disease caused by mutation of the prion protein gene (PRNP). In the present study, global expression patterns of the parietal cortex from a patient with G114V gCJD were analyzed using the Affymetrix Human Genome U133+ 2.0 chip with a commercial normal human parietal cortex RNA pool as a normal control. In total, 8,774 genes showed differential expression; among them 2,769 genes were upregulated and 6,005 genes were downregulated. The reliability of the results was confirmed using real-time RT-PCR assays. The most differentially expressed genes (DEGs) were involved in transcription regulation, ion transport, transcription, cell adhesion, and signal transduction. The genes associated with gliosis were upregulated and the genes marked for neurons were downregulated, while the transcription of the PRNP gene remained unaltered. A total of 169 different pathways exhibited significant changes in the brain of G114V gCJD. The most significantly regulated pathways included Alzheimer's and Parkinson's disease, oxidative phosphorylation, regulation of actin cytoskeleton, MAPK signaling and proteasome, which have previously been linked to prion diseases. In addition, we found some pathways that have rarely been explored in regards to prion diseases that were also significantly altered in G114V gCJD, such as axon guidance, gap junction and purine metabolism. The majority of the genes in the 10 most altered pathways were downregulated. The data of the present study provide useful insights into the pathogenesis of G114V gCJD and potential biomarkers for diagnostic and therapeutic purposes. IntroductionPrion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders in humans and animals, including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathies (BSEs) in cattle, and scrapie in sheep and goats. The conversion of prion protein (PrP), coded by the PRNP gene, from its cellular isoform PrP C to its pathogenic isoform PrP Sc through a post-translational process is considered the etiology of these diseases. As a result of the conversion, the portion of β-sheets within PrP is increased (from 3 to 45%) whereas that of α-helices decreases (from 42 to 30%), therefore causing PrP to become detergent insoluble and resistant to denaturant (isoform PrP Sc ) (1). The conversion also causes a series of histopathological changes, including the depositions of PrP Sc , spongiform degenerations, neuronal loss and astrogliosis.According to the pathomechanisms, CJD can be classified into sporadic CJD (sCJD), familial or genetic CJD (fCJD or gCJD) and iatrogenic CJD (iCJD). fCJD accounts for approximately 10-15% of all CJD cases, characterized by the genetic changes of PrP (2). To date, 56 different mutations, including residue substitutions, insertions and deletions, have been reported (3). For instance, proline to leucine mutation at the 102nd position (P102L) ...

show abstract

Section: Discussionmentioning

confidence: 99%

Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease

Tian

Chen

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

“…Previous experimental animal studies proposed that Cu, Zn-SOD knockout (Sod1 À/À ) caused an elevated oxidative stress status, resulting in various aging phenotypes such as muscle atrophy, 12 macular degeneration, 13 fat liver deposits, 14 hepatic carcinoma 15 and hemolytic anemia, 16 skin atrophy, 17 bone loss, 18,19 exacerbation of Alzheimer's disease, 20 and rotator cuff degeneration. 21 In humans, oxidative stress has been reported to be involved in many systemic diseases including Parkinson's disease, 22 Alzheimer's disease, 23 amyotrophic lateral sclerosis, 24 cardiovascular diseases, 25 cancer, 26,27 and ischemic disorders. 28,29 Oxygen free radical and antioxidant systems have also been demonstrated to be potentially important in the pathogenesis of ocular diseases such as cataract, 30 age-related macular degeneration, 13 glaucoma, 31 and dry eye disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of Oxidative Stress on the Conjunctiva in Cu, Zn-Superoxide Dismutase-1 (Sod1)–Knockout Mice

Kojima

Doğru

Ibrahim

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE.A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1 À/À mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression. METHODS. Fifty-week-old C57/B6 wild-type (WT) and Sod1À/À mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with antiMuc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-2 0 -deoxyguanosine antibodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR. RESULTS. The mean goblet cell density in the aged Sod1À/À mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1 À/À mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1 À/À mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1 À/À mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1 À/À mice was also significantly lower than the aged WT mice.CONCLUSIONS. Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1 À/À mice.

show abstract

“…[114][115][116] When excess ROS and reactive nitrogen species overcome endogenous antioxidant capacities, the state of metabolism is referred to as oxidative stress. 117 Subsequent oxidation of lipids, proteins, and DNA to toxic metabolites causes cellular dysfunction 118 ; ROS-mediated tissue damage has been positively correlated with TBI severity. 119,120 Oxidative stress after TBI predominantly manifests as lipid peroxidation, likely attributable to the brain's high polyunsaturated fatty acid (PUFA) content.…”

Section: Oxidative Stressmentioning

confidence: 99%

Repeated mild traumatic brain injury: potential mechanisms of damage

2016

Cell Transplant

View full text Add to dashboard Cite

Mild traumatic brain injury (mTBI) represents a significant public healthcare concern, accounting for the majority of all head injuries. While symptoms are generally transient, some patients go on to experience long-term cognitive impairments and additional mild impacts can result in exacerbated and persisting negative outcomes. To date, studies using a range of experimental models have reported chronic behavioral deficits in the presence of axonal injury and inflammation following repeated mTBI; assessments of oxidative stress and myelin pathology have thus far been limited. However, some models employed induced acute focal damage more suggestive of moderate-severe brain injury and are therefore not relevant to repeated mTBI. Given that the nature of mechanical loading in TBI is implicated in downstream pathophysiological changes, the mechanisms of damage and chronic consequences of single and repeated closed-head mTBI remain to be fully elucidated. This review covers literature on potential mechanisms of damage following repeated mTBI, integrating known mechanisms of pathology underlying moderate-severe TBIs, with recent studies on adult rodent models relevant to direct impact injuries rather than blast-induced damage. Pathology associated with excitotoxicity and cerebral blood flow-metabolism uncoupling, oxidative stress, cell death, blood-brain barrier dysfunction, astrocyte reactivity, microglial activation, diffuse axonal injury, and dysmyelination is discussed, followed by a summary of functional deficits and preclinical assessments of therapeutic strategies. Comprehensive characterization of the pathology underlying delayed and persisting deficits following repeated mTBI is likely to facilitate further development of therapeutic strategies to limit long-term sequelae.

show abstract

Oxidative Stress: Emerging Mitochondrial and Cellular Themes and Variations in Neuronal Injury

Cited by 134 publications

References 162 publications

Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease

Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease

Effects of Oxidative Stress on the Conjunctiva in Cu, Zn-Superoxide Dismutase-1 (Sod1)–Knockout Mice

Repeated mild traumatic brain injury: potential mechanisms of damage

Contact Info

Product

Resources

About