Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxidative stress plays a vital role in many pathological processes of the cardiovascular diseases. However, the underlying mechanism remains unclear, especially on a transcription factor (TF) level. In this study, a new method, concatenated tandem array of consensus transcription factor response elements (catTFREs), and an Illumina-based RNA-seq technology were integrated to systematically investigate the role of TFs in hydrogen peroxide (H
2
O
2
)-induced oxidative stress in cardiomyocytes; the damage was then rescued by Danhong injection (DHI), a Chinese standardized product approved for cardiovascular diseases treatment. The overall gene expression revealed cell apoptosis and DNA repair were vital for cardiomyocytes in resisting oxidative stress. By comprehensively integrating the transcription activity of TFs and their downstream target genes, an important TFs-target network were constructed and 13 TFs were identified as critical TFs in DHI-mediated protection in H
2
O
2
-induced oxidative stress. By using the integrated approach, seven TFs of these 13 TFs were also identified in melatonin-mediated protection in H
2
O
2
-induced damage. Furthermore, the transcription activity of
DNA-(apurinic or apyrimidinic site) lyase
(Apex1), Myocyte-specific enhancer factor 2D (Mef2d) and Pre B-cell
leukemia
transcription factor 3 (Pbx3) was further verified in pluripotent stem cell-derived cardiomyocytes. This research offers a new understanding of cardiomyocytes in response to H
2
O
2
-induced oxidative stress and reveals additional potential therapeutic targets. The combination of two parallel omics datasets (corresponding to the transcriptome and proteome) can reduce the noise in high-throughput data and reveal the fundamental changes of the biological process, making it suitable and reliable for investigation of critical targets in many other complicated pathological processes.
...
PMID:An integrated approach to identify critical transcription factors in the protection against hydrogen peroxide-induced oxidative stress by Danhong injection. 2882 48
Oxidative stress initiates harmful cellular responses, such as DNA damage and protein denaturation, triggering a series of cardiovascular disorders. Systematic investigations of the transcription factors (TFs) involved in oxidative stress can help reveal the underlying molecular mechanisms and facilitate the discovery of effective therapeutic targets in related diseases. In this study, an integrated strategy which integrated RNA-seq-based transcriptomics techniques and a newly developed concatenated tandem array of consensus TF response elements (catTFREs)-based proteomics approach and then combined with a network pharmacology analysis, was developed and this integrated strategy was used to investigate critical TFs in the protection of Yixin-shu (YXS), a standardized medical product used for ischaemic heart disease, against hydrogen peroxide (H
2
O
2
)-induced damage in cardiomyocytes. Importantly, YXS initiated biological process such as anti-apoptosis and DNA repair to protect cardiomyocytes from H
2
O
2
-induced damage. By using the integrated strategy,
DNA-(apurinic or apyrimidinic site) lyase
(Apex1), pre B-cell
leukemia
transcription factor 3 (Pbx3), and five other TFs with their functions involved in anti-oxidation, anti-apoptosis and DNA repair were identified. This study offers a new understanding of the mechanism underlying YXS-mediated protection against H
2
O
2
-induced oxidative stress in cardiomyocytes and reveals novel targets for oxidative stress-related diseases.
...
PMID:Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu. 2987 69
