Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain

Cui, Jiankun; Holmes, Eric H.; Greene, Thomas G.; Liu, Philip K.

doi:10.1096/fasebj.14.7.955

Cited by 151 publications

(139 citation statements)

References 64 publications

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“…For example, DNA strand breaks have been reported in neurons after reperfusion of ischemic tissue, well in advance of DNA fragmentation caused by the apoptotic process (Tobita et al, 1995;Chen et al, 1997;Cui et al, 2000). DNA damage also has been reported in other chronic neurodegenerative conditions such as Parkinson's (Robison and Bradley, 1984;Alam et al, 1997;Jenner, 1998), Huntington's, and Alzheimer's diseases (Gabbita et al, 1998;Mecocci et al, 1998;Lovell and Markesbery, 2001) and amyotrophic lateral sclerosis (ALS) (Robison and Bradley, 1984;Bogdanov et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Factor-κB Modulates the p53 Response in Neurons Exposed to DNA Damage

Aleyasin¹,

Cregan²,

Iyirhiaro³

et al. 2004

J. Neurosci.

111

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Previous studies have shown that DNA damage-evoked death of primary cortical neurons occurs in a p53 and cyclin-dependent kinasedependent (CDK) manner. The manner by which these signals modulate death is unclear. Nuclear factor-B (NF-B) is a group of transcription factors that potentially interact with these pathways. Presently, we show that NF-B is activated shortly after induction of DNA damage in a manner independent of the classic IB kinase (IKK) activation pathway, CDKs, ATM, and p53. Acute inhibition of NF-B via expression of a stable IB mutant, downregulation of the p65 NF-B subunit by RNA interference (RNAi), or pharmacological NF-B inhibitors significantly protected against DNA damage-induced neuronal death. NF-B inhibition also reduced p53 transcripts and p53 activity as measured by the p53-inducible messages, Puma and Noxa, implicating the p53 tumor suppressor in the mechanism of NF-B-mediated neuronal death. Importantly, p53 expression still induces death in the presence of NF-B inhibition, indicating that p53 acts downstream of NF-B. Interestingly, neurons cultured from p65 or p50 NF-B-deficient mice were not resistant to death and did not show diminished p53 activity, suggesting compensatory processes attributable to germline deficiencies, which allow p53 activation still to occur. In contrast to acute NF-B inhibition, prolonged NF-B inhibition caused neuronal death in the absence of DNA damage. These results uniquely define a signaling paradigm by which NF-B serves both an acute p53-dependent pro-apoptotic function in the presence of DNA damage and an anti-apoptotic function in untreated normal neurons.

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Section: Introductionmentioning

confidence: 99%

Nuclear Factor-κB Modulates the p53 Response in Neurons Exposed to DNA Damage

Aleyasin¹,

Cregan²,

Iyirhiaro³

et al. 2004

J. Neurosci.

111

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“…Another reason for reduced expression of PLCζ could be related to oxidative stress. DNA and RNA are common targets of reactive oxygen species [37] which might have a critical effect on embryo quality and pregnancy rates in IVF/ICSI treatments [38][39][40] and increased upon heat stress or in varicocele condition [30,41].…”

Section: Discussionmentioning

confidence: 99%

An association between sperm PLCζ levels and varicocele?

Janghorban-Laricheh

Ghazavi-Khorasgani

Tavalaee

et al. 2016

J Assist Reprod Genet

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Purpose We aimed to compare the expression of phospholipase C ζ (PLCζ), as one of the main sperm factors involved in oocyte activation, at both RNA and protein levels in fertile men and those with varicocele. Methods This study included 35 individuals with male factor infertility presenting primary infertility with grade II and III unilateral varicocele and 20 fertile men without varicocele. Semen parameters were assessed according to WHO 2010. Sperm DNA fragmentation, relative expression of PLCζ at messenger RNA, and protein levels were evaluated by sperm chromatin structure assay (SCSA), real-time PCR, and Western blot analysis, respectively. Results The results of this study reveal that the mean relative expression of PLCζ was significantly lower in individuals with varicocele compared to fertile men at both transcription and translation levels. In addition, the percentage of DNA fragmentation was significantly higher in infertile men with varicocele compared to fertile men. Conclusions The findings of the present study illustrate that one of the etiologies of reduced fertility associated with varicocele is the low expression of PLCζ. This effect could subsequently reduce the sperm ability to induce oocyte activation. Therefore, these results hold promise to modify our understanding of reproductive physiology of varicocele state.

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“…The peroxidation of cell membrane lipids and oxidative damage of nucleic acids can induce cell death [16]. Apoptosis is presumed to represent the final common pathway of cell injury mediated by oxidants, being induced by ROS either directly or indirectly through an alteration of the intracellular redox state and the expression of pro-inflammatory cytokines [17][18][19][20]. Because of the critical role of mitochondria in cell physiology, mitochondrial damage has been intensively investigated and it is thought to represent a major trigger for apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Evidence of oxidative injury during aging of the liver in a mouse model.

Colantoni

İdilman

Maria

et al. 2001

AGE

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The aim of the present study was to determine whether oxidative stress contributes to aging of the liver in a mouse model. Liver was obtained from young (3-5 months old) and aged (18-24 months old) mice. No age-induced gross changes in liver morphology were detected by light microscopy. Apoptosis was measured using the fragment end labeling of DNA for the immunohistochemical identification of the apoptotic nuclei. The total apoptotic cells represented 1% of the total cells in livers of young mice and 8% in those of aged mice. Among the total apoptotic cells in livers of aged animals, 15% were hepatocytes, 40% sinusoidal endothelial cells, and 45% bile duct cells. Hepatic lipid peroxidation, expressed as malonaldehyde levels, protein oxidation, measured by protein carbonyl content, and DNA oxidation, measured as 8-hydroxy-2'-deoxyguanosine (oxo(8)dG), were significantly increased in the livers of aged animals as compared to younger mice. The apoptotic cells presented elevated levels of oxidized DNA, detected by immunohistochemistry using an antibody directed against oxo(8)dG in serial sections. These results suggest that livers of aged animals presents evidence of increased oxidative injury and apoptosis. Because the apoptotic cells in the aged livers are mostly bile duct cells and sinusoidal endothelial cells, the cells most sensitive to oxidative stress injury, it can be hypothesized that reactive oxygen species-induced apoptosis in these cells contributes to the aging of the liver.

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Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain

Cited by 151 publications

References 64 publications

Nuclear Factor-κB Modulates the p53 Response in Neurons Exposed to DNA Damage

Nuclear Factor-κB Modulates the p53 Response in Neurons Exposed to DNA Damage

An association between sperm PLCζ levels and varicocele?

Evidence of oxidative injury during aging of the liver in a mouse model.

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