Oxidative RNA Damage and Neurodegeneration

Nunomura, Akihiko; Moreira, Paula I.; Takeda, Atsuhito; Smith, M. A.; Perry, George

doi:10.2174/092986707782794078

Cited by 84 publications

(68 citation statements)

References 109 publications

(230 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to inducing DNA, lipid, and protein damage, oxidative damage to protein-coding or -noncoding RNA may potentially cause errors in protein synthesis or dysregulation of gene expression. This has been proposed as an underlying mechanism of several human diseases, especially chronic degeneration in neurons (Nunomura et al 2007) Similarly, while protein oxidation has been implicated in a number of aging processes and diseases, most notably Alzheimer's disease (Levine et al 1994;Aksenov et al 2001;Balcz et al 2001), a clear link between protein oxidation and carcinogenesis has not been established. Lipid peroxidation results in the formation of reactive aldehydes, including malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), which demonstrate high reactivity with protein and DNA (Tuma 2002;Kikugawa, Taguchi, and Maruyama 1987;Nicholls et al 1992;Uchida and Stadtman 1993;Klaunig et al 1998).…”

Section: Ros In Carcinogenesismentioning

confidence: 99%

Oxidative Stress and Oxidative Damage in Carcinogenesis

2009

View full text Add to dashboard Cite

Carcinogenesis is a multistep process involving mutation and the subsequent selective clonal expansion of the mutated cell. Chemical and physical agents including those that induce reative oxygen species can induce and/or modulate this multistep process. Several modes of action by which carcinogens induce cancer have been identified, including through production of reactive oxygen species (ROS). Oxidative damage to cellular macromolecules can arise through overproduction of ROS and faulty antioxidant and/or DNA repair mechanisms. In addition, ROS can stimulate signal transduction pathways and lead to activation of key transcription factors such as Nrf2 and NF-kB. The resultant altered gene expression patterns evoked by ROS contribute to the carcinogenesis process. Recent evidence demonstrates an association between a number of single nucleotide polymorphisms (SNPs) in oxidative DNA repair genes and antioxidant genes with human cancer susceptibility. These aspects of ROS biology will be discussed in the context of their relationship to carcinogenesis.

show abstract

Section: Ros In Carcinogenesismentioning

confidence: 99%

Oxidative Stress and Oxidative Damage in Carcinogenesis

2009

View full text Add to dashboard Cite

show abstract

“…Finally, RNA is the most susceptible to oxidative damage, since it is single stranded, not protected by hydrogen bonding, and less protected by proteins. RNA damages may result in altered proteins or dysregulation of gene expression [41]. One of mitochondrial disorders is the myoclonus epilepsy with ragged red fibers (MERRF) syndrome that is linked to point mutations in the mitochondrial tRNALys gene [42, 43].…”

Section: Signalling Roles Of Ca2+ and Rosmentioning

confidence: 99%

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Martinc

Grabnar²,

Vovk³

2012

Current Neuropharmacology

View full text Add to dashboard Cite

Epilepsy is considered one of the most common neurological disorders. The focus of this review is the acquired form of epilepsy, with the development process consisting of three major phases, the acute injury phase, the latency epileptogenesis phase, and the phase of spontaneous recurrent seizures. Nowadays, an increasing attention is paid to the possible interrelationship between oxidative stress resulting in disturbance of physiological signalling roles of calcium and free radicals in neuronal cells and mitochondrial dysfunction, cell damage, and epilepsy. The positive stimulation of mitochondrial calcium signals by reactive oxygen species and increased reactive oxygen species generation resulting from increased mitochondrial calcium can lead to a positive feedback loop. We propose that calcium can pose both, physiological and pathological effects of mitochondrial function, which can lead in neuronal cell death and consequent epileptic seizures. Various antiepileptic drugs may impair the endogenous antioxidative ability to prevent oxidative stress. Therefore, some antiepileptic drugs, especially from the older generation, may trigger oxygen-dependent tissue injury. The prooxidative effects of these antiepileptic drugs might lead to enhancement of seizure activity, resulting in loss of their efficacy or apparent functional tolerance and undesired adverse effects. Additionally, various reactive metabolites of antiepileptic drugs are capable of covalent binding to macromolecules which may lead to deterioration of the epileptic seizures and systemic toxicity. Since neuronal loss seems to be one of the major neurobiological abnormalities in the epileptic brain, the ability of antioxidants to attenuate seizure generation and the accompanying changes in oxidative burden, further support an important role of antioxidants as having a putative antiepileptic potential.

show abstract

“…Both DNA and RNA oxidation were shown to be involved in various pathologic processes (e.g., neurodegenerative diseases, cancer, and cardiovascular diseases) (17,18), but nucleic-acid oxidation has received little attention in the pathogenesis of emphysema. Furthermore, nucleic-acid oxidation repair pathways have never been specifically investigated in emphysema.…”

mentioning

confidence: 99%

Cigarette Smoke Induces Nucleic-Acid Oxidation in Lung Fibroblasts

Deslée¹,

Adair-Kirk²,

Betsuyaku³

et al. 2010

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Oxidative stress is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD), but the molecular pathway connecting oxidative damage to tissue destruction remains to be fully defined. We suggest that reactive oxygen species (ROS) oxidatively damage nucleic acids, and this effect requires multiple repair mechanisms, particularly base excision pathway components 8-oxoguanine-DNA glycosylase (OGG1), endonuclease III homologue 1 (NTH1), and single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), as well as the nucleic acid-binding protein, Y-box binding protein 1 (YB1). This study was therefore designed to define the levels of nucleic-acid oxidation and expression of genes involved in the repair of COPD and in corresponding models of this disease. We found significant oxidation of nucleic acids localized to alveolar lung fibroblasts, increased levels of OGG1 mRNA expression, and decreased concentrations of NTH1, SMUG1, and YB1 mRNA in lung samples from subjects with very severe COPD compared with little or no COPD. Mice exposed to cigarette smoke exhibited a time-dependent accumulation of nucleic-acid oxidation in alveolar fibroblasts, which was associated with an increase in OGG1 and YB1 mRNA concentrations. Similarly, human lung fibroblasts exposed to cigarette smoke extract exhibited ROS-dependent nucleic-acid oxidation. The short interfering RNA (siRNA)-dependent knockdown of OGG1 and YB1 expression increased nucleic-acid oxidation at the basal state and after exposure to cigarette smoke. Together, our results demonstrate ROS-dependent, cigarette smoke-induced nucleic-acid oxidation in alveolar fibroblasts, which may play a role in the pathogenesis of emphysema.

show abstract

Oxidative RNA Damage and Neurodegeneration

Cited by 84 publications

References 109 publications

Oxidative Stress and Oxidative Damage in Carcinogenesis

Oxidative Stress and Oxidative Damage in Carcinogenesis

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Cigarette Smoke Induces Nucleic-Acid Oxidation in Lung Fibroblasts

Contact Info

Product

Resources

About