MicroRNA Regulation of Oxidative Stress‐Induced Cellular Senescence

Bu, Huaije; Wedel, Sophia; Cavinato, Maria; Jansen‐Dürr, Pidder

doi:10.1155/2017/2398696

Cited by 94 publications

(84 citation statements)

References 132 publications

(172 reference statements)

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“…Under OS, mitochondria suffer functional damage and accumulate in cells, releasing excessive ROS and apoptosis-inducing factors, which not only oxidatively damage DNA, protein, lipid, and other biological macromolecules, but also activate c-Jun N-terminal kinase (JNK), P38MAPK, DDR, and P53 pathways, ultimately leading to cell stress apoptosis and senescence 21,22,[49][50][51] . Therefore, accumulation of damaged mitochondria is an important cause of stress apoptosis and aging in BMSCs 52 .…”

Section: Discussionmentioning

confidence: 99%

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

et al. 2020

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Survival and stemness of bone marrow mesenchymal stem cells (BMSCs) in osteonecrotic areas are especially important in the treatment of early steroid-induced osteonecrosis of the femoral head (ONFH). We had previously used BMSCs to repair early steroid-induced ONFH, but the transplanted BMSCs underwent a great deal of stressinduced apoptosis and aging in the oxidative-stress (OS) microenvironment of the femoral-head necrotic area, which limited their efficacy. Our subsequent studies have shown that under OS, massive accumulation of damaged mitochondria in cells is an important factor leading to stress-induced apoptosis and senescence of BMSCs. The main reason for this accumulation is that OS leads to upregulation of protein 53 (P53), which inhibits mitochondrial translocation of Parkin and activation of Parkin's E3 ubiquitin ligase, which decreases the level of mitophagy and leads to failure of cells to effectively remove damaged mitochondria. However, P53 downregulation can effectively reverse this process. Therefore, we upregulated Parkin and downregulated P53 in BMSCs. We found that this significantly enhanced mitophagy in BMSCs, decreased the accumulation of damaged mitochondria in cells, effectively resisted stress-induced BMSCs apoptosis and senescence, and improved the effect of BMSCs transplantation on early steroidinduced ONFH.

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Section: Discussionmentioning

confidence: 99%

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

et al. 2020

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“…Many senescence‐associated miRNA signatures have been identified and reported . The present study mainly focused on studying the effect of kallistatin on differential regulation of 2 miRNAs, Let‐7g and miR‐34a in endothelial senescence.…”

Section: Discussionmentioning

confidence: 99%

Kallistatin attenuates endothelial senescence by modulating Let‐7g‐mediated miR‐34a‐SIRT1‐eNOS pathway

Guo

Chao

2018

J Cellular Molecular Medi

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Kallistatin, a plasma protein, protects against vascular and organ injury. This study is aimed to investigate the role and mechanism of kallistatin in endothelial senescence. Kallistatin inhibited H2O2‐induced senescence in human endothelial cells, as indicated by reduced senescence‐associated‐β‐galactosidase activity, p16INK 4a and plasminogen activator inhibitor‐1 expression, and elevated telomerase activity. Kallistatin blocked H2O2‐induced superoxide formation, NADPH oxidase levels and VCAM‐1, ICAM‐1, IL‐6 and miR‐34a synthesis. Kallistatin reversed H2O2‐mediated inhibition of endothelial nitric oxide synthase (eNOS), SIRT1, catalase and superoxide dismutase (SOD)‐2 expression, and kallistatin alone stimulated the synthesis of these antioxidant enzymes. Moreover, kallistatin's anti‐senescence and anti‐oxidant effects were attributed to SIRT1‐mediated eNOS pathway. Kallistatin, via interaction with tyrosine kinase, up‐regulated Let‐7g, whereas Let‐7g inhibitor abolished kallistatin's effects on miR‐34a and SIRT1/eNOS synthesis, leading to inhibition of senescence, oxidative stress and inflammation. Furthermore, lung endothelial cells isolated from endothelium‐specific kallistatin knockout mice displayed marked reduction in mouse kallistatin levels. Kallistatin deficiency in mouse endothelial cells exacerbated senescence, oxidative stress and inflammation compared to wild‐type mouse endothelial cells, and H2O2 treatment further magnified these effects. Kallistatin deficiency caused marked reduction in Let‐7g, SIRT1, eNOS, catalase and SOD‐1 mRNA levels, and elevated miR‐34a synthesis in mouse endothelial cells. These findings indicate that endogenous kallistatin through novel mechanisms protects against endothelial senescence by modulating Let‐7g‐mediated miR‐34a‐SIRT1‐eNOS pathway.

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“…The function of RBCs is to carry oxygen throughout the body by binding to hemoglobin. Autoxidation of hemoglobin makes RBCs more susceptible to oxidative stress (OS) damage [4]. Recent reports highlight the emerging role of RBCs in several biological processes of importance to metabolic functions, including diabetes mellitus and its complications [5,6].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of miR144 and miR451 Expression in the Circulating Human Erythrocytes from the African American Adults

2020

ARC Journal of Diabetes and Endocrinology

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There are several mechanisms that drive the aging process in the human body. Cellular senescence which leads to permanent cell growth arrest and oxidative stress are examples of aging promoting mechanisms. Moreover, genetics and epigenetic play important roles in accelerating and/or delaying the onset of the aging process. miRNAs are important players in controlling OS, aging, and cellular senescence. The purpose of this study was to evaluate circulating erythrocyte miR-451 and miR-144 expression as potential biomarker of cell aging. Blood samples were collected from consented volunteers and miRNAs were isolated from a control group and Type 2 Diabetes Mellitus. Taqman primers were used for detection and quantification of miR-144 and miR-451. Erythrocytes were further sub-fractionated into young, mid and old age by using discontinuous Percoll gradient. miRNA's were isolated from erythrocytes using miRNA Isolation kit. The miR-451 expression was significantly down-regulated in old cells in T2DM group, while miR-144 expression was significantly up-regulated in old cells in T2DM. The findings of this study are consistent with our previous report of increase expression of miR-451 and miR-144 as the cell gets old. The current findings suggest that miR-451 and miR-144 may have a role in aging process.

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MicroRNA Regulation of Oxidative Stress‐Induced Cellular Senescence

Cited by 94 publications

References 132 publications

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

Kallistatin attenuates endothelial senescence by modulating Let‐7g‐mediated miR‐34a‐SIRT1‐eNOS pathway

Dysregulation of miR144 and miR451 Expression in the Circulating Human Erythrocytes from the African American Adults

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