NR8383 Alveolar Macrophage Toxic Growth Arrest by Hydrogen Peroxide Is Associated with Induction of Growth-Arrest and DNA Damage-Inducible GenesGADD45andGADD153

Patton, Geoffrey W.; Paciga, June E.; Shelley, Sue A.

doi:10.1006/taap.1997.8227

Cited by 14 publications

(6 citation statements)

References 38 publications

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“…36 Several reports indicate that ROS can up-regulate the transcription of CHOP. [37][38][39][40][41][42] However, contradictory data exist, reporting down-regulation of CHOP by H 2 O 2 in neuronal cells. 43 In addition, up-regulation of CHOP by superoxide dismutase was found in MCF7 cells.…”

Section: Discussionmentioning

confidence: 99%

Expression and Function of C/EBP Homology Protein (GADD153) in Podocytes

Bek

Bayer

Müller

et al. 2006

The American Journal of Pathology

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Podocytes are crucial for the permeability of the glomerular filtration barrier. In glomerular disease, however, reactive oxygen species (ROS) may be involved in podocyte injury and subsequent proteinuria. Here, we describe ROS-dependent gene induction in differentiated podocytes stimulated with H(2)O(2) or xanthine/xanthine-oxidase. Superoxide anions and H(2)O(2) increased mRNA and protein expression of GAS5 (growth arrest-specific protein 5) and CHOP (C/EBP homology protein). Cultured podocytes overexpressing CHOP showed increased generation of superoxide anions compared to controls. In addition, the expression of alpha(3)/beta(1) integrins, crucial for cell-matrix interaction of podocytes, was down-regulated, leading to increased cell-matrix adhesion and cell displacement. The altered cell-matrix adhesion was antagonized by the ROS scavenger 1,3-dimethyl-2-thiourea, and the increase in cell displacement could be mimicked by stimulating untransfected podocytes with puromycin, an inductor of ROS. We next performed immunohistochemical staining of human kidney tissue (normal, membranous nephropathy, focal segmental glomerulosclerosis, and minimal change nephropathy) as well as sections from rats with puromycin nephrosis, a model of minimal change nephropathy. CHOP was weakly expressed in podocytes of control kidneys but up-regulated in most proteinuric human kidneys and in rat puromycin nephrosis. Our data suggest that CHOP-via increased ROS generation-regulates cell-matrix adhesion of podocytes in glomerular disease.

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Section: Discussionmentioning

confidence: 99%

Expression and Function of C/EBP Homology Protein (GADD153) in Podocytes

Bek

Bayer

Müller

et al. 2006

The American Journal of Pathology

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“…Both genes are induced whenever a cell is stressed by damage to genomic DNA (42), including treatment of cells with hydrogen peroxide, a chemical that readily forms oxygen radicals within the cell leading to production of thymine glycols on genomic DNA (43). Transcription-coupled repair of oxidative DNA damage has been identified as an important function of BRCA1.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 Effects on the Cell Cycle and the DNA Damage Response Are Linked to Altered Gene Expression

MacLachlan¹,

Somasundaram²,

Sgagias³

et al. 2000

Journal of Biological Chemistry

211

184

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The breast and ovarian cancer susceptibility gene product BRCA1 has been reported to be expressed in a cell cycle-dependent manner; possess transcriptional activity; associate with several proteins, including the p53 tumor suppressor; and play an integral role in certain types of DNA repair. We show here that ectopic expression of BRCA1 using an adenovirus vector (Ad-BRCA1) leads to dephosphorylation of the retinoblastoma protein accompanied by a decrease in cyclin-dependent kinase activity. Flow cytometric analysis on Ad-BRCA1-infected cells revealed a G 1 or G 2 phase accumulation. High density cDNA array screening of colon, lung, and breast cancer cells identified several genes affected by BRCA1 expression in a p53-independent manner, including DNA damage response genes and genes involved in cell cycle control. Notable changes included induction of the GADD45 and GADD153 genes and a reduction in cyclin B1 expression. Therefore, BRCA1 has the potential to modulate the expression of genes and function of proteins involved in cell cycle control and DNA damage response pathways.

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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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NR8383 Alveolar Macrophage Toxic Growth Arrest by Hydrogen Peroxide Is Associated with Induction of Growth-Arrest and DNA Damage-Inducible GenesGADD45andGADD153

Cited by 14 publications

References 38 publications

Expression and Function of C/EBP Homology Protein (GADD153) in Podocytes

Expression and Function of C/EBP Homology Protein (GADD153) in Podocytes

BRCA1 Effects on the Cell Cycle and the DNA Damage Response Are Linked to Altered Gene Expression

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

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