MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs

Zhang, Huaping; Zhao, Zhenxiang; Pang, Xue-Fen; Yang, Jian; Hou, Yu; Zhang, Yinhong; Zhou, Hui; Zhao, Jiahui

doi:10.1016/j.toxlet.2017.07.216

Cited by 49 publications

(46 citation statements)

References 52 publications

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“…ROS have been identified to act as a major trigger of Ec apoptosis (42). Zhang et al (43) revealed that miR-34a/sirtuin-1/foxo3a exerts an important function in genistein in preventing ox-LdL-induced oxidative damage in HUVECs. According to these findings, the present study examined whether the knockdown of miR-34a ameliorates ox-LdL-induced apoptosis via modulating ROS, and examined the protective effects of the downregulation of miR-34a on oxidative injury.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells

Zhang

et al. 2018

Int J Mol Med

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Oxidized low‑density lipoprotein (ox‑LDL) promotes endothelial cell dysfunction, which is a primary risk factor for the development of atherosclerosis. A previous study reported that microRNA (miRNA/miR)‑34a is upregulated in atherosclerotic samples. However, its function and underlying mechanisms remain to be fully elucidated. In the present study, miRNA microarray analysis was performed to investigate the miRNA expression profile in atherosclerotic plaque tissues and examine the role of miR‑34a in ox‑LDL‑induced apoptosis of human umbilical vein endothelial cells (HUVECs). Cell viability, apoptosis and protein expression was determined by a cell counting kit‑8 assay, flow cytometry and western blot analysis, respectively. It was observed that miR‑34a was upregulated in atherosclerotic plaque tissues and that ox‑LDL treatment significantly increased the levels of miR‑34a in a dose‑dependent manner in the HUVECs. The knockdown of miR‑34a increased the protein expression of B‑cell lymphoma 2 (Bcl‑2) and cell viability, improved mitochondrial membrane potential, and decreased the activity of caspase‑3, number of apoptotic cells and release of cytochrome c from mitochondria in the ox‑LDL‑treated HUVECs. The results also demonstrated that the knockdown of miR‑34a suppressed the levels of ox‑LDL‑induced reactive oxygen species (ROS) in HUVECs. Additionally, it was found that Bcl‑2 was a target of miR‑34a in HUVECs, and that silencing Bcl‑2 abrogated the protective effects of the downregulation of miR‑34a on ox‑LDL‑induced apoptosis. These data indicated that the knockdown of miR‑34a protected against ox‑LDL apoptosis and ROS in HUVECs via inhibiting the mitochondrial apoptotic pathway, suggesting it may offer potential as a biomarker in the clinical diagnosis and as a target for the treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells

Zhang

et al. 2018

Int J Mol Med

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“…On the other hand, the reduced transcription of the miR-34a by antioxidant agents such as resveratrol, statins and genistein in various cell types is well documented [ 59 , 60 ]. Our data appear to be in agreement with the current literature showing that the increase in miR-34a levels in chondrocytes exposed to H 2 O 2 was reverted by pre-treatment of the cells with taurine, in particular at a concentration of 200 μM.…”

Section: Discussionmentioning

confidence: 99%

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

Cheleschi

Palma

Pascarelli

et al. 2017

IJMS

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Oxidative stress and the overproduction of reactive oxygen species (ROS) play an important role in the pathogenesis of osteoarthritis (OA). Accumulating evidence has demonstrated the involvement of microRNAs (miRNAs) dysregulation in disease development and progression. In this study, we evaluated the effect of oxidative stress on miR-146a and miR-34a expression levels in human OA chondrocytes cultures stimulated by H2O2. Mitochondrial ROS production and cell apoptosis were detected by flow cytometry. The antioxidant enzymes SOD-2, CAT, GPx, the transcriptional factor NRF2 and the selected miRNAs were analyzed by qRT-PCR. The H2O2-induced oxidative stress was confirmed by a significant increase in superoxide anion production and of the apoptotic ratio. Furthermore, H2O2 significantly up-regulated the expression levels of SOD-2, CAT, GPx and NRF2, and modulated miR-146a and miR-34a gene expression. The same analyses were carried out after pre-treatment with taurine, a known antioxidant substance, which, in our experience, counteracted the H2O2-induced effect. In conclusion, the induction of oxidative stress affected cell apoptosis and the expression of the enzymes involved in the oxidant/antioxidant balance. Moreover, we demonstrated for the first time the modification of miR-146a and miR-34a in OA chondrocytes subjected to H2O2 stimulus and we confirmed the antioxidant effect of taurine.

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“…By activating FOXO/MsSOD pathway, SIRT1 increases the expression of manganese superoxide dismutase (MnSOD) and catalase, counteracting oxidative stress and promoting damage repair (Gu et al, 2016). SIRT1 also increases the expression of MnSOD by deacetylating p53, thus enhancing cellular antioxidant capacity (Brunet et al, 2004;Zhang et al, 2017;Ren et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

SIRT1 Activation by Natural Phytochemicals: An Overview

et al. 2020

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Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD + as a cofactor. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity. SIRT1 has been implicated in both tumorigenic and anticancer processes, and is reported to regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders of the metabolism. Via regulation of p53 deacetylation and modulation of autophagy, SIRT1 is implicated in cellular response to caloric restriction and lifespan extension. In recent years, scientific interest focusing on the identification of SIRT1 modulators has led to the discovery of novel small molecules targeting SIRT1 activity. This review will examine compounds of natural origin recently found to upregulate SIRT1 activity, such as polyphenolic products in fruits, vegetables, and plants including resveratrol, fisetin, quercetin, and curcumin. We will also discuss the potential therapeutic effects of these natural compounds in the prevention and treatment of human disorders, with particular emphasis on their metabolic impact.

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MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs

Cited by 49 publications

References 52 publications

Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells

Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

SIRT1 Activation by Natural Phytochemicals: An Overview

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