JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2021
·Vol. 35
·期 10
·e22880
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IF 3.652
Haijuan Jing,Chuan Wang,Liang Zhao,Jing Cheng,Pengyu Qin,Hongqi Lin
Previous studies have shown that propofol (PPF) plays a protective role in ischemia–reperfusion (I/R) in multiple organs and tissues. This study was aimed to explore the mechanism of PPF in ameliorating myocardial ischemia-reperfusion injury (MIRI). MIRI model was established with Sprague–Dawley rats, and PPF pretreatment was performed before reperfusion. Creatine kinase isoform (CK-MB), lactate dehydrogenase (LDH), and hematoxylin and eosin stain were used to evaluate the severity of MIRI. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to simulate I/R injury in vitro. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess MALAT1 and microRNA (miR)−206 expressions. Autophagy-related 3 (ATG3), LC3BⅡ/LC3BⅠ, and Beclin-1 expression were examined by western blot. Apoptosis was monitored using flow cytometry. Interaction between MALAT1 and miR-206 was determined by bioinformatics analysis, dual-luciferase reporter gene assay, RIP assay, and RNA pull-down assay. PPF pretreatment remarkably reduced CK-MB level, LDH level, myocardial infarct size, and LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression in the rats with MIRI, and repressed the apoptosis of H9c2 cells exposed to H/R. PPF pretreatment markedly suppressed MALAT1 expression and enhanced miR-206 expression in both in vivo and in vitro models. MiR-206 was identified as a target of MALAT1 in cardiomyocytes, and MALAT1 could increase the expression of ATG3. Additionally, the upregulation of MALAT1 partially reversed the protective effect of PPF on cardiomyocytes in vitro. PPF modulated MALAT1/miR-206/ATG3 axis to protect cardiomyocytes against I/R injury.
研究领域:
心脏病学
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药理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Guowei Zhu,Junqing Yang,Dongzhi Ran,Ying Luo,Yanyi Wang,Wenjia Guo,Xiaodan Tan,Xiaobing Zhao,Yuanhong Gan,Huafeng Yin,Hong Wang
Non-alcoholic fatty liver disease (NAFLD) has become the fastest-growing etiology of cirrhosis and hepatocellular carcinoma. No Food and Drug Administration (FDA)-approved pharmacotherapy currently exists, underscoring the urgent need for novel regulatory circuits that can be translated into druggable targets. Here we demonstrate that autophagic flux is severely impaired and lipid accumulation markedly exacerbated in livers of NAFLD mouse models and in hepatocytes challenged with free fatty acid (FFA). Knock-down of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) elevated miR-690 abundance, restored autophagic flux, and attenuated intracellular lipid deposition. Consistently, silencing methyltransferase-like 3 (METTL3) decreased MALAT1, thereby increasing miR-690 and producing the same protective phenotype, whereas METTL3 over-expression elicited the opposite effects. Mechanistically, METTL3 directly bound MALAT1 and installed N6-methyladenosine (m6A) modifications that enhanced MALAT1 stability and expression. Up-regulated MALAT1 subsequently sponged miR-690, leading to its functional depletion, autophagosome–lysosome fusion blockade, and aggravated lipid retention. Collectively, the METTL3-m6A/MALAT1/miR-690 axis orchestrates autophagy and lipid homeostasis, operationalizing an “m6A–long non-coding RNA (lncRNA)–microRNA (miRNA)” regulatory paradigm in NAFLD and offering an epitranscriptomic perspective on disease pathogenesis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2020
·
IF 1.574
Yongxia Cheng,Jingchao Li,Chong Wang,Heran Yang,Ying Wang,Tao Zhan,Sufen Guo,Jun Liang,Yuxin Bai,Jianbo Yu,Guibo Liu
Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications of diabetes mellitus independent of hypertension, coronary disease, and other heart diseases. The development of DCM is multifactorial and hard to detect at an early stage. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is emerging as a regulator of DCM, the underlying mechanism of its role in DCM has not been elaborated yet. In this study, we established a mouse DCM model via streptozocin injection as evidenced by cell hypertrophy and cell apoptosis of myocardial tissue, and found that Malat1 expression was upregulated in the myocardium in DCM mice. Meanwhile, elevated expression of pro-apoptotic factors p53, p21, cleaved caspase 3, cleaved caspase 9 and BAX, and down-regulation of anti-apoptotic BCL-2 were observed in DCM myocardium. We further investigated the effect of Malat1 on cardiomyocytes under high glucose condition by silencing Malat1 with its specific short-hairpin RNA. Like in vivo, expression of Malat1 in cardiomyocytes was notably raised, remarkable cell apoptosis and changes in apoptosis-related factors were also observed following high glucose treatment. Besides, we validated that Malat1 acted as a sponge of miR-181a-5p. Inhibition of miR-181a-5p could, at least partially, abolish Malat1 knockdown-induced alteration in cardiomyocytes. In addition, p53, a critical regulator of apoptosis, was validated to be a downstream target of miR-181a-5p. In summary, our findings reveal that Malat1 knockdown attenuates high glucose-induced cardiomyocyte apoptosis via releasing miR-181a-5p, and this mechanism may provide us with new diagnosis target of DCM.
研究领域:
分子生物学
·
心脏病学
·
糖尿病
·
非编码RNA
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）