Limits...
Transcriptome analysis of human OXR1 depleted cells reveals its role in regulating the p53 signaling pathway.

Yang M, Lin X, Rowe A, Rognes T, Eide L, Bjørås M - Sci Rep (2015)

Bottom Line: The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown.In total, in non-treated and hydrogen peroxide exposed HeLa cells, OXR1 depletion resulted in down-regulation of 554 genes and up-regulation of 253 genes.In summary, OXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species and modulate cell cycle and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, Norway.

ABSTRACT
The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown. We employed RNA sequencing to examine the role of human OXR1 for genome wide transcription regulation. In total, in non-treated and hydrogen peroxide exposed HeLa cells, OXR1 depletion resulted in down-regulation of 554 genes and up-regulation of 253 genes. These differentially expressed genes include transcription factors (i.e. HIF1A, SP6, E2F8 and TCF3), antioxidant genes (PRDX4, PTGS1 and CYGB) and numerous genes of the p53 signaling pathway involved in cell-cycle arrest (i.e. cyclin D, CDK6 and RPRM) and apoptosis (i.e. CytC and CASP9). We demonstrated that OXR1 depleted cells undergo cell cycle arrest in G2/M phase during oxidative stress and increase protein expression of the apoptosis initiator protease CASP9. In summary, OXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species and modulate cell cycle and apoptosis.

No MeSH data available.


Related in: MedlinePlus

Gene ontology (GO) analysis of the deferentially expressed genes in hOXR1 depleted HeLa cells.The number of DEGs in each category was compared between non-treated (NT) and H2O2 treated (R0h) HeLa cells. (a) Cellular components. (b) Biochemical processes. (c) Molecular function.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4663793&req=5

f2: Gene ontology (GO) analysis of the deferentially expressed genes in hOXR1 depleted HeLa cells.The number of DEGs in each category was compared between non-treated (NT) and H2O2 treated (R0h) HeLa cells. (a) Cellular components. (b) Biochemical processes. (c) Molecular function.

Mentions: Next, we performed Gene Ontology (GO) analysis of the DEGs. The GO covers three domains: cellular components, biological processes and molecular functions. A large percentage of the DEGs are associated to the membrane and organelle categories (Fig. 2a). Among the biological processes, the largest clusters include biological regulation, cellular processes, metabolic processes and response to stimulus and signaling (Fig. 2b). The hOXR1-affected transcriptome may imply a molecular function in binding, catalytic activities, enzyme regulators, molecular transducers, nucleic acid binding, receptor activities and transporter activities (Fig. 2c). Previously, we have identified two hOXR1-regulated antioxidant genes (GPX2 and HO-1)10. In this study, three additional genes are identified in the cluster of “antioxidant activity”: peroxiredoxin 4 (PRDX4), prostaglandin-endoperoxide synthase 1(PTGS1) and cytoglobin (CYGB). CYGB is a hemoglobin induced protein expressed in response to oxidative stress and involved in protection against oxidative stress induced apoptosis and cell death by scavenging ROS1112. Notably, depletion of hOXR1 caused down-regulation of CYGB and PTGS1 as well as HO-1 under both oxidative stress and normal physiology (Supplementary Fig. S5).


Transcriptome analysis of human OXR1 depleted cells reveals its role in regulating the p53 signaling pathway.

Yang M, Lin X, Rowe A, Rognes T, Eide L, Bjørås M - Sci Rep (2015)

Gene ontology (GO) analysis of the deferentially expressed genes in hOXR1 depleted HeLa cells.The number of DEGs in each category was compared between non-treated (NT) and H2O2 treated (R0h) HeLa cells. (a) Cellular components. (b) Biochemical processes. (c) Molecular function.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663793&req=5

f2: Gene ontology (GO) analysis of the deferentially expressed genes in hOXR1 depleted HeLa cells.The number of DEGs in each category was compared between non-treated (NT) and H2O2 treated (R0h) HeLa cells. (a) Cellular components. (b) Biochemical processes. (c) Molecular function.
Mentions: Next, we performed Gene Ontology (GO) analysis of the DEGs. The GO covers three domains: cellular components, biological processes and molecular functions. A large percentage of the DEGs are associated to the membrane and organelle categories (Fig. 2a). Among the biological processes, the largest clusters include biological regulation, cellular processes, metabolic processes and response to stimulus and signaling (Fig. 2b). The hOXR1-affected transcriptome may imply a molecular function in binding, catalytic activities, enzyme regulators, molecular transducers, nucleic acid binding, receptor activities and transporter activities (Fig. 2c). Previously, we have identified two hOXR1-regulated antioxidant genes (GPX2 and HO-1)10. In this study, three additional genes are identified in the cluster of “antioxidant activity”: peroxiredoxin 4 (PRDX4), prostaglandin-endoperoxide synthase 1(PTGS1) and cytoglobin (CYGB). CYGB is a hemoglobin induced protein expressed in response to oxidative stress and involved in protection against oxidative stress induced apoptosis and cell death by scavenging ROS1112. Notably, depletion of hOXR1 caused down-regulation of CYGB and PTGS1 as well as HO-1 under both oxidative stress and normal physiology (Supplementary Fig. S5).

Bottom Line: The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown.In total, in non-treated and hydrogen peroxide exposed HeLa cells, OXR1 depletion resulted in down-regulation of 554 genes and up-regulation of 253 genes.In summary, OXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species and modulate cell cycle and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, Norway.

ABSTRACT
The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown. We employed RNA sequencing to examine the role of human OXR1 for genome wide transcription regulation. In total, in non-treated and hydrogen peroxide exposed HeLa cells, OXR1 depletion resulted in down-regulation of 554 genes and up-regulation of 253 genes. These differentially expressed genes include transcription factors (i.e. HIF1A, SP6, E2F8 and TCF3), antioxidant genes (PRDX4, PTGS1 and CYGB) and numerous genes of the p53 signaling pathway involved in cell-cycle arrest (i.e. cyclin D, CDK6 and RPRM) and apoptosis (i.e. CytC and CASP9). We demonstrated that OXR1 depleted cells undergo cell cycle arrest in G2/M phase during oxidative stress and increase protein expression of the apoptosis initiator protease CASP9. In summary, OXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species and modulate cell cycle and apoptosis.

No MeSH data available.


Related in: MedlinePlus