The in vivo gene expression signature of oxidative stress

Han, Eun Soo; Muller, Florian L.; Pérez, Viviana; Qi, Wenbo; Liang, Huiyun; Liu, Xi; Fu, Chunxiao; Doyle, Erin L.; Hickey, Morgen; Cornell, John E.; Epstein, Charles J.; Roberts, L. Jackson; Remmen, Holly Van; Richardson, Arlan

doi:10.1152/physiolgenomics.00239.2007

Cited by 217 publications

(167 citation statements)

References 85 publications

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“…Several Nrf2 target genes, as well as other genes involved in apoptosis, DNA damage, oxidative stress, and protein folding, are induced by nifurtimox and nifurtimox plus TM combination treatment. These results are comparable to a study that investigated the in vivo gene expression of oxidative stress in mice treated with diquat, a redox cycler, and Sod1-/-mice (40). Similar to our results in nifurtimox and TM treated medulloblastoma cells, up-regulation in several antioxidant genes, including Srxn1, Gclc, Txn2, and HMOX-1, in SOD1-/-mice has been shown (40).…”

Section: Discussionsupporting

confidence: 91%

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma

Koto

Lescault²,

Brard³

et al. 2011

Int J Oncol

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Abstract. Medulloblastoma, a neuroectodermal tumor arising in the cerebellum, is the most common brain tumor found in children. We recently showed that nifurtimox induces production of reactive oxygen species (ROS) and subsequent apoptosis in neuroblastoma cells both in vitro and in vivo. Tetrathiomolybdate (TM) has been shown to decrease cell proliferation by inhibition of superoxide dismutase-1 (SOD1). Since both nifurtimox and TM increase ROS levels in cells, we investigated whether the combination of nifurtimox and TM would act synergistically in medulloblastoma cell lines (D283, DAOY). Genome-wide transcriptional analysis, by hybridizing RNA isolated from nifurtimox and TM alone or in combination treated and control cells (D283) on Affymetrix exon array gene chips was carried out to further confirm synergy. We show that nifurtimox and TM alone and in combination decreased cell viability and increased ROS levels synergistically. Examination of cell morphology following drug treatment (nifurtimox + TM) and detection of caspase-3 activation via Western blotting indicated that cell death was primarily due to apoptosis. Microarray data from cells treated with nifurtimox and TM validated the induction of oxidative stress, as many Nrf2 target genes (HMOX1, GCLM, SLC7A11 and SRXN1) (p<10 -5 ) were upregulated. Other genes related to apoptosis, oxidative stress, DNA damage, protein folding and nucleosome formation were differentially involved in cells following treatment with nifurtimox + TM. Taken together, our results suggest nifurtimox and TM act synergistically in medulloblastoma cells in vitro, and that this combination warrants further studies as a new treatment for medulloblastoma.

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Section: Discussionsupporting

confidence: 91%

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma

Koto

Lescault²,

Brard³

et al. 2011

Int J Oncol

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“…2 Shortest path co-citation network of genes for which transcript levels were significantly altered following extend fast generated using BiblioSphere software. following the extended fast, is increased in parallel with increased CDKN1A in response to oxidative and other cellular stresses (Han et al 2008) and in liver following treatment with glucocorticoids; hormones that help to regulate blood glucose during fasting (Wong et al 2010). Expression of clusterin at the level of mRNA is, at least in part, dependent on CDKN1A (Chen et al 2004).…”

Section: Effects Of Extended Fast On Pbmc Transcription Profilesmentioning

confidence: 99%

Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism

et al. 2014

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“…This activation results in upregulation of p53 and down-regulation of B cell lymphoma-2, ultimately leading to apoptotic cell death. [33][34][35] It has also been reported that H 2 O 2 is also capable of inducing the apoptosis of RGC-5 cells through the caspase-independent apoptotic pathway involving the upregulation of AIF and cleaved PARP proteins. 36) In our study, the levels of various apoptotic proteins in lysates harvested from control untreated cultures and cultures exposed to 800 μM H 2 O 2 in the presence or absence of R. verniciflua extract were determined by Western blot analysis for PARP, cleaved caspase-3, and caspase-9 (Fig.…”

Section: Effect Of R Verniciflua Extract On Lipid Peroxidationmentioning

confidence: 99%

Preparative Isolation and Purification of Neuroprotective Compounds from <i>Rhus verniciflua</i> by High Speed Counter-Current Chromatography

Choi

Lee

et al. 2012

Biological & Pharmaceutical Bulletin

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In the present study, extracts from Rhus verniciflua were demonstrated to significantly attenuate the negative effects of hydrogen peroxide (H 2 O 2 ) on transformed retinal ganglion cell line (RGC-5 cells), indicating that they may be protective against oxidative stress-induced retinal degeneration. The inclusion of R. verniciflua in the culture was found to both reduce the levels of reactive oxygen species (ROS) present and lessen the up-regulation of apoptotic proteins such as cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9. Active compounds were also successfully isolated from R. verniciflua using high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3.5 : 5 : 3.5 : 5, v/v). Using this method, we successfully separated 252.1 mg of fustin at a purity of over 93.09%, 51.2 mg of fisetin at a purity of over 95.45%, 39.7 mg of sulfuretin at a purity of over 95.17%, and 10.7 mg of butein at a purity of over 95.01% from 1.5 g of R. verniciflua extract. The chemical structures of these compounds were elucidated by chemical and spectral analyses. There isolated compounds also significantly attenuated the negative effects of H 2 O 2 on RGC-5 cells. Results therefore suggest that, due to its anti-oxidative and anti-apoptotic effects, R. verniciflua could be used as a lead substance for the treatment of retinal diseases such as glaucoma.

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The in vivo gene expression signature of oxidative stress

Abstract: doi: 10.1152/physiolgenomics.00239.2007 You might find this additional info useful... Supplementary material for this article can be found at

Cited by 217 publications

References 85 publications

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma

Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism

Preparative Isolation and Purification of Neuroprotective Compounds from <i>Rhus verniciflua</i> by High Speed Counter-Current Chromatography

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