A Gene Regulatory Network Shows Oxidative Stress Response as the Underlying Mechanism of Sperm Chromatin Remodeling in Aging Males

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins. The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.

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Ling-Gui-Zhu-Gan Decoction Protects H9c2 Cells against H2O2-Induced Oxidative Injury via Regulation of the Nrf2/Keap1/HO-1 Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8860603 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Xiang Wang ◽

Tongjuan Tang ◽

Mengting Zhai ◽

Ruirui Ge ◽

Liang Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Stress Response ◽

Caspase 3 ◽

Underlying Mechanism ◽

Oxidative Stress Response ◽

Control Group ◽

H9c2 Cells ◽

Model Group ◽

Blank Control Group

Objectives. Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment for heart failure, and it showed significant anti-inflammatory potential in our previous studies. However, its ability to ameliorate heart failure through regulation of oxidative stress response is still unknown. This study was aimed to investigate the protective effect of LGZGD-containing serum on H2O2-induced oxidative injury in H9c2 cells and explore the underlying mechanism. Methods. Eighteen rats were randomly divided into two groups: the blank control group and LGZGD group. The LGZGD group rats were administrated with 8.4 g/kg/d LGZGD for seven consecutive days through gavage, while the blank control group rats were given an equal volume of saline. The serum was extracted from all the rats. To investigate the efficacy and the underlying mechanism of LGZGD, we categorized the H9c2 cells into groups: the control group, model group, normal serum control (NSC) group, LGZGD group, LGZGD + all-trans-retinoic acid (ATRA) group, and ATRA group. Malonedialdehyde (MDA) and superoxide dismutase (SOD) were used as markers for oxidative stress. Dichlorodihydrofluorescin diacetate (DCFH-DA) staining was used to measure the levels of reactive oxygen species (ROS). The apoptosis rate was detected using flow cytometry. The expression levels of pro-caspase-3, cleaved-caspase-3, Bcl-2, Bax, Keap1, Nrf2, and HO-1 were measured using western blotting. The mRNA levels of Keap1, Nrf2, and HO-1 were measured using RT-qPCR. Results. The LGZGD attenuated injury to H9c2 cells and reduced the apoptosis rate. It was also found to upregulate the SOD activity and suppress the formation of MDA and ROS. The expression levels of pro-caspase-3 and Bcl-2 were significantly increased, while those of cleaved-caspase-3 and Bax were decreased in the LGZGD group compared with the model group. As compared with the model group, the LGZGD group demonstrated decreased Keap1 protein expression and significantly increased Nrf2 nuclear expression and Nrf2-mediated transcriptional activity. ATRA was found to reverse the LGZGD-mediated antioxidative and antiapoptotic effect on injured H9c2 cells induced by H2O2. Conclusion. Our results demonstrated that LGZGD attenuated the H2O2-induced injury to H9c2 cells by inhibiting oxidative stress and apoptosis via the Nrf2/Keap1/HO-1 pathway. These observations suggest that LGZGD might prevent and treat heart failure through regulation of the oxidative stress response.

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Correction: Velvet domain protein VosA represses the zinc cluster transcription factor SclB regulatory network for Aspergillus nidulans asexual development, oxidative stress response and secondary metabolism

PLoS Genetics ◽

10.1371/journal.pgen.1007638 ◽

2018 ◽

Vol 14 (8) ◽

pp. e1007638

Author(s):

Karl G. Thieme ◽

Jennifer Gerke ◽

Christoph Sasse ◽

Oliver Valerius ◽

Sabine Thieme ◽

...

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Stress Response ◽

Secondary Metabolism ◽

Aspergillus Nidulans ◽

Regulatory Network ◽

Oxidative Stress Response ◽

Asexual Development ◽

Zinc Cluster ◽

Domain Protein

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Identification of Four Oxidative Stress-Responsive MicroRNAs, miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p, in Hepatocellular Carcinoma

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/5189138 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 21

Author(s):

Yong Wan ◽

Ruixia Cui ◽

Jingxian Gu ◽

Xing Zhang ◽

Xiaohong Xiang ◽

...

Keyword(s):

Oxidative Stress ◽

Hepatocellular Carcinoma ◽

Stress Response ◽

Clinical Investigation ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Oxidative Stress Response ◽

Rank Aggregation ◽

Integrated Analysis ◽

Pathway Enrichment Analysis

Increasing evidence suggests that oxidative stress plays an essential role during carcinogenesis. However, the underlying mechanism between oxidative stress and carcinogenesis remains unknown. Recently, microRNAs (miRNAs) are revealed to be involved in oxidative stress response and carcinogenesis. This study aims to identify miRNAs in hepatocellular carcinoma (HCC) cells which might involve in oxidative stress response. An integrated analysis of miRNA expression signature was performed by employing robust rank aggregation (RRA) method, and four miRNAs (miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p) were identified as the oxidative stress-responsive miRNAs. Pathway enrichment analysis suggested that these four miRNAs played an important role in antiapoptosis process. Our data also revealed miR-34a-5p and miR-1915-3p, but not miR-150-3p and miR-638, were regulated by p53 in HCC cell lines under oxidative stress. In addition, clinical investigation revealed that these four miRNAs might be involved in oxidative stress response by targeting oxidative stress-related genes in HCC tissues. Kaplan-Meier analysis showed that these four miRNAs were associated with patients’ overall survival. In conclusion, we identified four oxidative stress-responsive miRNAs, which were regulated by p53-dependent (miR-34a-5p and miR-1915-3p) and p53-independent pathway (miR-150-3p and miR-638). These four miRNAs may offer new strategy for HCC diagnosis and prognosis.

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Transcriptome analysis reveals the oxidative stress response in Saccharomyces cerevisiae

RSC Advances ◽

10.1039/c4ra14600j ◽

2015 ◽

Vol 5 (29) ◽

pp. 22923-22934 ◽

Cited By ~ 11

Author(s):

Hongwei Zhao ◽

Jingyu Chen ◽

Jingjing Liu ◽

Beizhong Han

Keyword(s):

Oxidative Stress ◽

Saccharomyces Cerevisiae ◽

Stress Response ◽

Transcriptome Analysis ◽

Regulatory Network ◽

Oxidative Stress Response ◽

Oxidation Stress

A global regulatory network involving the response to the oxidation stress inSaccharomyces cerevisiaewas revealed in this study.

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RECTA: Regulon Identification Based on Comparative Genomics and Transcriptomics Analysis

10.1101/261453 ◽

2018 ◽

Author(s):

Xin Chen ◽

Anjun Ma ◽

Adam McDermaid ◽

Hanyuan Zhang ◽

Chao Liu ◽

...

Keyword(s):

Transcriptional Regulation ◽

Stress Response ◽

Comparative Genomics ◽

Gene Regulatory Network ◽

Lactococcus Lactis ◽

Regulatory Network ◽

Acid Stress ◽

Orthologous Genes ◽

Gene Regulatory ◽

Acid Stress Response

ABSTRACTRegulons, which serve as co-regulated gene groups contributing to the transcriptional regulation of microbial genomes, have the potential to aid in understanding of underlying regulatory mechanisms. In this study, we designed a novel computational pipeline, RECTA, for regulon prediction related to the gene regulatory network under certain conditions. To demonstrate the effectiveness of this tool, we implemented RECTA onLactococcus lactisMG1363 data to elucidate acid-response regulons.Lactococcus lactisis one of the most important Gram-positive lactic acid-producing bacteria, widely used in food industry and has been proved to have advantages in oral delivery of drug and vaccine. The pipeline carries out differential gene expression, gene co-expression analysis,cis-regulatory motif finding, and comparative genomics to predict and validate regulons related to acid stress response. A total of 51 regulonswere identified, 14 of which have computational-verified significance. Among these 14 regulons, five of them were computationally predicted to be connected with acid stress response with (i) known transcriptional factors in MEME suite database successfully mapped inLactococcus lactisMG1363; and (ii) differentially expressed genes between pH values of 6.5 (control) and 5.1 (treatment). Validated by 36 literature confirmed acid stress response related proteins and genes, 33 genes inLactococcus lactisMG1363 were found having orthologous genes using BLAST, associated to six regulons. An acid response related regulatory network was constructed, involving two trans-membrane proteins, eight regulons (llrA, llrC, hllA, ccpA, NHP6A,rcfB, regulons #8 and #39), nine functional modules, and 33 genes with orthologous genes known to be associated to acid stress. Our RECTA pipeline provides an effective way to construct a reliable gene regulatory network through regulon elucidation. The predicted response pathways could serve as promising candidates for better acid tolerance engineering inLactococcus lactis. RECTA has strong application power and can be effectively applied to other bacterial genomes where the elucidation of the transcriptional regulation network is needed.

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