Targeting of miR-96-5p by catalpol ameliorates oxidative stress and hepatic steatosis in LDLr-/- mice via p66shc/cytochrome C cascade

Zhang, Yukun; Wang, Changyuan; Lu, Jiawei; Jin, Yue; Xu, Canyao; Meng, Qiang; Liu, Qi; Dong, Deshi; Ma, Xiaodong; Liu, Kexin; Sun, Huijun

doi:10.18632/aging.102721

Cited by 28 publications

(13 citation statements)

References 49 publications

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“…Cheng et al demonstrated that miR-421 overexpression significantly decreased hepatic MnSOD and CAT expression and subsequently aggravated oxidative damage upon NAFLD stimulation via directly targeting sirtuin 3 [ 53 ]. In addition, Zhang et al recently showed that miR-96-5p was capable of suppressing p66shc expression, thereby reducing oxidative stress and hepatic steatosis [ 54 ]. Based on these contexts, we thus investigated the function of miR-137-3p, a potential antioxidant molecule in the liver, during NAFLD progression [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα

Sheng

et al. 2021

Analytical Cellular Pathology

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Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and can develop to nonalcoholic steatohepatitis and later hepatic cirrhosis with a high prevalence to hepatocellular carcinoma. Oxidative stress and chronic hepatic inflammation are implicated in the pathogenesis of NAFLD. MicroRNA-137-3p (miR-137-3p) are associated with oxidative stress and inflammation; however, its role and mechanism in NAFLD remain unclear. Mice were fed with a high-fat diet (HFD) for 24 weeks to establish the NAFLD model. To overexpress or suppress hepatic miR-137-3p expression, mice were intraperitoneally injected with the agomir, antagomir, or respective controls of miR-137-3p at a dose of 100 mg/kg weekly for 6 consecutive weeks before the mice were sacrificed. To validate the involvement of AMP-activated protein kinase alpha (AMPKα) or cAMP-specific phosphodiesterase 4D (PDE4D), HFD mice were intraperitoneally injected with 20 mg/kg compound C or 0.5 mg/kg rolipram every other day for 8 consecutive weeks before the mice were sacrificed. Hepatic miR-137-3p expression was significantly decreased in mice upon HFD stimulation. miR-137-3p agomir alleviated, while miR-137-3p antagomir facilitated HFD-induced oxidative stress, inflammation, and hepatic dysfunction in mice. Mechanistically, we revealed that miR-137-3p is directly bound to the 3 ′ -untranslated region of PDE4D and subsequently increased hepatic cAMP level and protein kinase A activity, thereby activating the downstream AMPKα pathway. In summary, miR-137-3p improves NAFLD through activating AMPKα and it is a promising therapeutic candidate to treat NAFLD.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα

Sheng

et al. 2021

Analytical Cellular Pathology

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“…Cytochrome C participates in ROS production and mitochondrial apoptosis. Zhang et al found that the upregulation of miR-96-5p ameliorated NAFLD through inhibition of the p66shc/cytochrome C cascade [78]. The brief information of the above-mentioned miRNAs has been summarized in Table 3.…”

Section: The Role Of Mirnas In Modulation Of Oxidative Stress and Er Stress In Nafldmentioning

confidence: 99%

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

2021

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Nonalcoholic fatty liver disease (NAFLD), or, more accurately, metabolic associated fatty liver disease, accounts for a large proportion of chronic liver disorders worldwide and is closely associated with other conditions such as cardiovascular disease, obesity, and type 2 diabetes mellitus. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and can progress to cirrhosis and, eventually, also hepatocellular carcinoma. The morbidity and mortality associated with NAFLD are increasing rapidly year on year. Consequently, there is an urgent need to understand the etiology and pathogenesis of NAFLD and identify effective therapeutic targets. MicroRNAs (miRNAs), important epigenetic factors, have recently been proposed to participate in NAFLD pathogenesis. Here, we review the roles of miRNAs in lipid metabolism, inflammation, apoptosis, fibrosis, hepatic stellate cell activation, insulin resistance, and oxidative stress, key factors that contribute to the occurrence and progression of NAFLD. Additionally, we summarize the role of miRNA-enriched extracellular vesicles in NAFLD. These miRNAs may comprise suitable therapeutic targets for the treatment of this condition.

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“…Catalpol is an iridoid glucoside derived from Rehmannia glutinosa that exerts anti-cancer, neuroprotective, anti-inflammatory, antioxidant stress, and mitochondrial function regulatory effects (Jiang and Zhang, 2020;Yan et al, 2020;Zhang et al, 2020). CTL can inhibit H 2 O 2 -induced cardiomyocyte apoptosis through the mitochondria-dependent caspase pathway.…”

Section: Catalpol (Ctl)mentioning

confidence: 99%

Regulation of Mitochondrial Quality Control by Natural Drugs in the Treatment of Cardiovascular Diseases: Potential and Advantages

Chang

Zhang

Zhao

et al. 2020

Front. Cell Dev. Biol.

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Mitochondria are double-membraned cellular organelles that provide the required energy and metabolic intermediates to cardiomyocytes. Mitochondrial respiratory chain defects, structure abnormalities, and DNA mutations can affect the normal function of cardiomyocytes, causing an imbalance in intracellular calcium ion homeostasis, production of reactive oxygen species, and apoptosis. Mitochondrial quality control (MQC) is an important process that maintains mitochondrial homeostasis in cardiomyocytes and involves multi-level regulatory mechanisms, such as mitophagy, mitochondrial fission and fusion, mitochondrial energy metabolism, mitochondrial antioxidant system, and mitochondrial respiratory chain. Furthermore, MQC plays a role in the pathological mechanisms of various cardiovascular diseases (CVDs). In recent years, the regulatory effects of natural plants, drugs, and active ingredients on MQC in the context of CVDs have received significant attention. Effective active ingredients in natural drugs can influence the production of energy-supplying substances in the mitochondria, interfere with the expression of genes associated with mitochondrial energy requirements, and regulate various mechanisms of MQC modulation. Thus, these ingredients have therapeutic effects against CVDs. This review provides useful information about novel treatment options for CVDs and development of novel drugs targeting MQC.

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Targeting of miR-96-5p by catalpol ameliorates oxidative stress and hepatic steatosis in LDLr-/- mice via p66shc/cytochrome C cascade

Cited by 28 publications

References 49 publications

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Regulation of Mitochondrial Quality Control by Natural Drugs in the Treatment of Cardiovascular Diseases: Potential and Advantages

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