DNA Damage,gadd153Expression, and Cytotoxicity in Plateau-Phase Renal Proximal Tubular Epithelial Cells Treated with a Quinol Thioether

Jeong, Jeongmi K.; Dybing, Erik; Søderlund, Erik J.; Brunborg, Gunnar; Holme, Jørn A.; Lau, Serrine S.; Monks, Terrence J.

doi:10.1006/abbi.1997.9969

Cited by 14 publications

(12 citation statements)

References 44 publications

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“…The effect of oxidative stress on the expression of ERstress proteins have been studied in various non-neuronal cell culture systems with divergent results (Dreher et al 1995b;Crawford et al 1996;Guyton et al 1996;Jeong et al 1996;Jeong et al 1997;Patton et al 1997;Outinen et al 1998;Timblin et al 1998;Zhang et al 1999;Abramova et al 2000;Towndrow et al 2000). Whereas the expression of ER-resident stress proteins tended to be up-regulated in these studies performed with non-neuronal cells, grp78, grp94 and gadd153 mRNA levels were decreased upon H 2 O 2 exposure of our neuronal cell cultures, suggesting that neurones react to oxidative stress in a somewhat different way compared to non-neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

Peroxidative stress selectively down‐regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction

Paschen

Mengesdorf

Althausen

et al. 2001

Journal of Neurochemistry

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Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Here, we investigated the effect of peroxide exposure on the expression of genes coding for cytoplasmic and endoplasmic reticulum (ER) stress proteins. Primary neuronal cell cultures were exposed to H 2 O 2 for 6 h and mRNA levels of hsp70, grp78, grp94, gadd153 were evaluated by quantitative PCR. In addition, peroxide-induced changes in protein synthesis and cell viability were investigated. Peroxide treatment of cells triggered an almost 12-fold increase in hsp70 mRNA levels, but a signi®cant decrease in grp78, grp94 and gadd153 mRNA levels. To establish whether peroxide exposure blocks the ER-resident stress response, cells were also exposed to thapsigargin (Tg, a speci®c inhibitor of ER Ca 21 -ATPase) which has been shown to elicit the ER stress response. Tg exposure induced 7.2-fold, 3.6-fold and 8.8-fold increase in grp78, grp94 and gadd153 mRNA levels, respectively. However, after peroxide pre-exposure, the Tginduced effect on grp78, grp94 and gadd153 mRNA levels was completely blocked. The results indicate that oxidative damage causes a selective down-regulation of the neuronal stress response activated under conditions of ER dysfunction. This down-regulation was only observed in cultures exposed to peroxide levels which induced severe suppression of protein synthesis and cell injury, implying a causative link between peroxide-induced down-regulation of ER stress response system and development of neuronal cell injury. These observations could have implications for our understanding of the mechanisms underlying neuronal cell injury in pathological states of the brain associated with oxidative damage, including Alzheimer's disease where the neuronal stress response activated under conditions of ER dysfunction has been shown to be down-regulated. Down-regulation of ER stress response may increase the sensitivity of neurones to an otherwise nonlethal form of stress.

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Section: Discussionmentioning

confidence: 99%

Peroxidative stress selectively down‐regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction

Paschen

Mengesdorf

Althausen

et al. 2001

Journal of Neurochemistry

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“…p53 is a zinc finger transcription factor that induces the transcription of a variety of proteins including p21, Gadd45, and Gaddl53 (50,51), which are involved in cell cycle arrest and DNA repair. Transcription of p53 is inhibited by adenovirus E 1 B protein (103), Epstein-Barr virus E6 proteins (138), WT 1 expression (81), bcl-2 (13), and bfl (19).…”

Section: P53mentioning

confidence: 99%

Review Article: Apoptosis in the Kidney

Davis

Ryan

1998

Toxicol Pathol

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Apoptosis is a highly regulated mechanism of cell death. Although apoptosis has a functional role in normal development and tissue homeostasis, aberrant triggering of the process by toxicants may lead to abnormal function or disease. Low level exposures to toxicants that induce apoptosis in kidney may therefore create a critical disturbance in kidney homeostasis, contributing to renal neoplasia or renal disease. In this report, we review the involvement of apoptosis in normal kidney development and in renal disease and discuss some of the toxicants and molecular factors involved in regulation of the process in renal cells.

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“…One such gene, Gadd153 (also known as chop), encodes a member of the CCAAT\enhancer-binding protein (C\EBP) family of transcription factors. Originally isolated based on its induction by UV-C irradiation [1], Gadd153 has subsequently been shown to be highly induced in a variety of stress paradigms that result in growth arrest or DNA damage, including genotoxic agents [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], calcium ionophore [17], nutrient depletion [15,[18][19][20], oxidative stress [21][22][23], reductive stress [24,25], endoplasmic reticulum stress [26][27][28] and the acute-phase response [29,30]. GADD153 (where GADD stands for growth arrest and DNA damage-inducible protein) has been implicated in the commitment to, or implementation of, growth arrest or cell death ; microinjection of GADD153 induces 3T3 cells to arrest at the G " \S boundary [31], while ectopic expression of GADD153 causes M1 myeloblastic leukaemia cells to undergo apoptosis [32].…”

Section: Introductionmentioning

confidence: 99%

Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response

Fawcett

Martindale

Guyton

et al. 1999

Biochemical Journal

375

229

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Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family and is transcriptionally activated by cellular stress signals. We recently demonstrated that arsenite treatment of rat pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA expression, controlled in part through binding of C/EBPβ and two uncharacterized protein complexes to the C/EBP–ATF (activating transcription factor) composite site in the Gadd153 promoter. In this report, we identified components of these additional complexes as two ATF/CREB (cAMP-responsive-element-binding protein) transcription factors having differential binding activities dependent upon the time of arsenite exposure. During arsenite treatment of PC12 cells, we observed enhanced binding of ATF4 to the C/EBP–ATF site at 2 h as Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as Gadd153 expression declined. We further demonstrated that ATF4 activates, while ATF3 represses, Gadd153 promoter activity through the C/EBP–ATF site. ATF3 also repressed ATF4-mediated transactivation and arsenite-induced activation of the Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB family are involved in the cellular stress response, and that regulation of stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered, sequential binding of multiple transcription factor complexes to the C/EBP–ATF composite site.

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DNA Damage,gadd153Expression, and Cytotoxicity in Plateau-Phase Renal Proximal Tubular Epithelial Cells Treated with a Quinol Thioether

Cited by 14 publications

References 44 publications

Peroxidative stress selectively down‐regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction

Peroxidative stress selectively down‐regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction

Review Article: Apoptosis in the Kidney

Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response

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