scholarly journals Resveratrol Attenuates Aflatoxin B1-Induced ROS Formation and Increase of m6A RNA Methylation

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 677 ◽  
Author(s):  
Jiamin Wu ◽  
Zhending Gan ◽  
Ruhao Zhuo ◽  
Lili Zhang ◽  
Tian Wang ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
Caspase 3 ◽  
Basal Diet ◽  
Hepatic Function ◽  
Redox Status ◽  
Rna Methylation ◽  
Ros Accumulation ◽  
Serum Aspartate Aminotransferase ◽  
Ros Formation ◽  
M6a Rna Methylation

Aflatoxin B1 (AFB1) is one of the most dangerous mycotoxins in both humans and animals. Regulation of resveratrol is essential for the inhibition of AFB1-induced oxidative stress and liver injury. Whether N6-methyladenosine (m6A) mRNA methylation participates in the crosstalk between resveratrol and AFB1 is unclear. The objective of this study was to investigate the effects of AFB1 and resveratrol in m6A RNA methylation and their crosstalk in the regulation of hepatic function in mice. Thirty-two C57BL/6J male mice were randomly assigned to a CON (basal diet), RES (basal diet + 500 mg/kg resveratrol), AFB1 (basal diet + 600 μg/kg aflatoxin B1), and ARE (basal diet + 500 mg/kg resveratrol and 600 μg/kg aflatoxin B1) group for 4 weeks of feeding (n = 8/group). Briefly, redox status, apoptosis, and m6A modification in the liver were assessed. Compared to the CON group, the AFB1 group showed increased activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), prevalent vacuolization and cell edema, abnormal redox status, imbalance apoptosis, and especially, the higher expression of cleaved-caspase-3 protein. On the contrary, resveratrol ameliorated adverse hepatic function, via increasing hepatic antioxidative capacity and inhibiting the expression of cleaved-caspase-3 protein. Importantly, we noted that reactive oxygen species (ROS) content could be responsible for the alterations of m6A modification. Compared to the CON group, the AFB1 group elevated the ROS accumulation, which led to the augment in m6A modification, whereas dietary resveratrol supplementation decreased ROS, followed by the reduction of m6A levels. In conclusion, our findings indicated that resveratrol decreased AFB1-induced ROS accumulation, consequently contributing to the alterations of m6A modification, and eventually impacting on the hepatic function.

scholarly journals Cross-Talk between Oxidative Stress and m6A RNA Methylation in Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-26
Author(s):  
Baishuang Yang ◽  
Qiong Chen
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Tumor Development ◽  
Rna Modification ◽  
Posttranscriptional Control ◽  
Rna Methylation ◽  
Cancer Cell Death ◽  
Ros Accumulation ◽  
M6a Rna Methylation

Oxidative stress is a state of imbalance between oxidation and antioxidation. Excessive ROS levels are an important factor in tumor development. Damage stimulation and excessive activation of oncogenes cause elevated ROS production in cancer, accompanied by an increase in the antioxidant capacity to retain redox homeostasis in tumor cells at an increased level. Although moderate concentrations of ROS produced in cancer cells contribute to maintaining cell survival and cancer progression, massive ROS accumulation can exert toxicity, leading to cancer cell death. RNA modification is a posttranscriptional control mechanism that regulates gene expression and RNA metabolism, and m6A RNA methylation is the most common type of RNA modification in eukaryotes. m6A modifications can modulate cellular ROS levels through different mechanisms. It is worth noting that ROS signaling also plays a regulatory role in m6A modifications. In this review, we concluded the effects of m6A modification and oxidative stress on tumor biological functions. In particular, we discuss the interplay between oxidative stress and m6A modifications.

Danshensu Rescues Ischemia/Reperfusion Caused Human Hepatocyte Death

2018 ◽  
Vol 17 (2) ◽  
pp. 117-121
Author(s):  
Sun Maw-Sheng ◽  
Liang Chun-Ya ◽  
Hsieh Po-Chun ◽  
Kuo Chan-Yen
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Oxygen Species ◽  
Good Strategy ◽  
Ros Accumulation ◽  
Dichlorofluorescin Diacetate ◽  
Hepatocyte Damage ◽  
Hepatocyte Death

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apoptotic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR.

scholarly journals The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mohammad Burhan Uddin ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Noncoding Rna ◽  
Rna Modification ◽  
Oncogenic Signaling ◽  
Aberrant Expression ◽  
Rna Methylation ◽  
Rna Molecules ◽  
M6a Rna Methylation ◽  
Oncogenic Signaling Pathways

AbstractThe m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

scholarly journals N6-Methyladenosine RNA modification in cerebrospinal fluid as a novel potential diagnostic biomarker for progressive multiple sclerosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fei Ye ◽  
Tianzhu Wang ◽  
Xiaoxin Wu ◽  
Jie Liang ◽  
Jiaoxing Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Clustering Analysis ◽  
Roc Curves ◽  
Progressive Multiple Sclerosis ◽  
Rna Modification ◽  
Diagnostic Model ◽  
Consensus Clustering ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background Progressive multiple sclerosis (PMS) is an uncommon and severe subtype of MS that worsens gradually and leads to irreversible disabilities in young adults. Currently, there are no applicable or reliable biomarkers to distinguish PMS from relapsing–remitting multiple sclerosis (RRMS). Previous studies have demonstrated that dysfunction of N6-methyladenosine (m6A) RNA modification is relevant to many neurological disorders. Thus, the aim of this study was to explore the diagnostic biomarkers for PMS based on m6A regulatory genes in the cerebrospinal fluid (CSF). Methods Gene expression matrices were downloaded from the ArrayExpress database. Then, we identified differentially expressed m6A regulatory genes between MS and non-MS patients. MS clusters were identified by consensus clustering analysis. Next, we analyzed the correlation between clusters and clinical characteristics. The random forest (RF) algorithm was applied to select key m6A-related genes. The support vector machine (SVM) was then used to construct a diagnostic gene signature. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of the diagnostic model. In addition, CSF samples from MS and non-MS patients were collected and used for external validation, as evaluated by an m6A RNA Methylation Quantification Kit and by real-time quantitative polymerase chain reaction. Results The 13 central m6A RNA methylation regulators were all upregulated in MS patients when compared with non-MS patients. Consensus clustering analysis identified two clusters, both of which were significantly associated with MS subtypes. Next, we divided 61 MS patients into a training set (n = 41) and a test set (n = 20). The RF algorithm identified eight feature genes, and the SVM method was successfully applied to construct a diagnostic model. ROC curves revealed good performance. Finally, the analysis of 11 CSF samples demonstrated that RRMS samples exhibited significantly higher levels of m6A RNA methylation and higher gene expression levels of m6A-related genes than PMS samples. Conclusions The dynamic modification of m6A RNA methylation is involved in the progression of MS and could potentially represent a novel CSF biomarker for diagnosing MS and distinguishing PMS from RRMS in the early stages of the disease.

The potential role of m6A RNA methylation in diabetic retinopathy

2021 ◽  
pp. 108616
Author(s):  
Nidhi Kumari ◽  
Aditi Karmakar ◽  
Md Maqsood Ahamad Khan ◽  
Senthil Kumar Ganesan
Keyword(s):  
Diabetic Retinopathy ◽  
Potential Role ◽  
Rna Methylation ◽  
M6a Rna Methylation

scholarly journals Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuechai Chen ◽  
Jianan Wang ◽  
Muhammad Tahir ◽  
Fangfang Zhang ◽  
Yuanyuan Ran ◽  
...  
Keyword(s):  
Intervertebral Disc Degeneration ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Degradation Process ◽  
Human Diseases ◽  
Rna Modification ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
The Impact

AbstractAutophagy is a conserved degradation process crucial to maintaining the primary function of cellular and organismal metabolism. Impaired autophagy could develop numerous diseases, including cancer, cardiomyopathy, neurodegenerative disorders, and aging. N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells, and the fate of m6A modified transcripts is controlled by m6A RNA binding proteins. m6A modification influences mRNA alternative splicing, stability, translation, and subcellular localization. Intriguingly, recent studies show that m6A RNA methylation could alter the expression of essential autophagy-related (ATG) genes and influence the autophagy function. Thus, both m6A modification and autophagy could play a crucial role in the onset and progression of various human diseases. In this review, we summarize the latest studies describing the impact of m6A modification in autophagy regulation and discuss the role of m6A modification-autophagy axis in different human diseases, including obesity, heart disease, azoospermatism or oligospermatism, intervertebral disc degeneration, and cancer. The comprehensive understanding of the m6A modification and autophagy interplay may help in interpreting their impact on human diseases and may aid in devising future therapeutic strategies.

Sign in / Sign up

Export Citation Format

Share Document