The mitomiR/Bcl-2 axis affects mitochondrial function and autophagic vacuole formation in senescent endothelial cells

Giuliani, Angelica; Cirilli, Ilenia; Prattichizzo, Francesco; Mensà, Emanuela; Fulgenzi, Gianluca; Sabbatinelli, Jacopo; Graciotti, Laura; Olivieri, Fabiola; Procopio, Antonio; Tiano, Luca; Rippo, Maria Rita

doi:10.18632/aging.101591

Cited by 30 publications

(28 citation statements)

References 58 publications

(77 reference statements)

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“…Several studies have documented that some mitomiRs promote mitochondrial dysfunction via Bcl-2 downregulation [98,99]. Bcl-2 is an antioxidant and antiapoptotic mitochondrial protein and regulates mitochondrial fission/fusion [100,101].…”

Section: Mirnas That Inhibit Angiogenesismentioning

confidence: 99%

“…The mitomiR-induced Bcl-2 deregulation may lead to a state of dysfunctional mitochondria, increased oxidative stress, chronic low-grade inflammation, and increased apoptosis rates in angiogenesis-related diseases. Giuliani et al found that mitomiR-181a, -34a, and -146a, were upregulated and localized to mitochondria and downregulated Bcl-2 in human aging endothelial cells [98]. Further, overexpression of these mitomiRs was found to decrease Bcl-2 expression, leading to mitochondrial permeability transition pore opening, activation of caspase-1 and 3, and cell apoptosis [98].…”

Section: Mirnas That Inhibit Angiogenesismentioning

confidence: 99%

“…Giuliani et al found that mitomiR-181a, -34a, and -146a, were upregulated and localized to mitochondria and downregulated Bcl-2 in human aging endothelial cells [98]. Further, overexpression of these mitomiRs was found to decrease Bcl-2 expression, leading to mitochondrial permeability transition pore opening, activation of caspase-1 and 3, and cell apoptosis [98]. MitomiRs has been demonstrated to inhibit angiogenesis and vascularization [102]; however, the molecular mechanisms involved in mitomiRs-inhibited angiogenesis, with particular emphasis on those associated with cardiovascular disease, need further investigation.…”

Section: Mirnas That Inhibit Angiogenesismentioning

confidence: 99%

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Mitochondrial MiRNA in Cardiovascular Function and Disease

Song

Zhang

2019

Cells

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MicroRNAs (miRNAs) are small noncoding RNAs functioning as crucial post-transcriptional regulators of gene expression involved in cardiovascular development and health. Recently, mitochondrial miRNAs (mitomiRs) have been shown to modulate the translational activity of the mitochondrial genome and regulating mitochondrial protein expression and function. Although mitochondria have been verified to be essential for the development and as a therapeutic target for cardiovascular diseases, we are just beginning to understand the roles of mitomiRs in the regulation of crucial biological processes, including energy metabolism, oxidative stress, inflammation, and apoptosis. In this review, we summarize recent findings regarding how mitomiRs impact on mitochondrial gene expression and mitochondrial function, which may help us better understand the contribution of mitomiRs to both the regulation of cardiovascular function under physiological conditions and the pathogenesis of cardiovascular diseases.

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Section: Mirnas That Inhibit Angiogenesismentioning

confidence: 99%

Section: Mirnas That Inhibit Angiogenesismentioning

confidence: 99%

Section: Mirnas That Inhibit Angiogenesismentioning

confidence: 99%

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Mitochondrial MiRNA in Cardiovascular Function and Disease

Song

Zhang

2019

Cells

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“…Cell viability, total cellular and mitochondrial ROS levels and mitochondrial Permeability transition pore (mPTP) opening were evaluated as previously described [ 26 , 27 ]. Flow cytometry coupled with appropriate fluorescent probes was conducted on a Guava EasyCyte flow cytometer equipped with GuavaSoft 2.7 software and an excitation source at 488 nm (Merck Millipore, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract

Cirilli¹,

Orlando²,

Marcheggiani³

et al. 2020

Antioxidants

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Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.

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“…Under the guidance of Prof. Maria Rita Rippo, the research group has also highlighted mechanisms of resistance to programmed cell death of senescent cells and on those that regulate the differentiation of mesenchymal stromal cells (MSCs) which show alterations in their proliferative and differentiating capacity in elderly [77]. In particular, for the first time we suggested and demonstrated that mito-miRs (mitochondria resident or associated to mitochondrial membranes) are modulated and can control expression of Bcl-2 family members and the oxidative and energetic status in aging cells thus contributing to their resistance to pro-apoptotic stimuli, pro-inflammatory phenotype and altered autophagy [29,30,67]. Furthermore, our group demonstrated that FasL, whose circulating levels decrease progressively during aging [36], is modulated in post-menopausal women [37] and play a pivotal role in bone homeostasis inhibiting MSCs differentiation in adipocytes and inducing their proliferation [66].…”

Section: The New Program On Aging and Age-related Diseases (Ards): Idmentioning

confidence: 98%

The Experimental Pathology at Ancona: 50 Years of Exciting and Pioneering Research on Human Pathology

Olivieri

Rippo

Graciotti

et al. 2020

The First Outstanding 50 Years of “Università Politecnica Delle Marche”

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Half century ago, a few academic pioneers founded the laboratories of experimental and ultrastructural pathology in Ancona. From this origin, a new phase of experimental studies developed aimed at translational and clinical research up to the present, when our group is internationally recognized for its fundamental contributions in gerontological research and molecular diagnostic pathology. Since the desire of immortality and of eternal youth seems to be as old as mankind, in the future we plan to focus our scientific research on Regenerative Medicine and Rejuvenation strategies. This is the most ambitious aim in the framework of the world aging population. We do not know whether we would achieve these results by ourselves. We are confident that, as in the past, new generations of scientist of the school of experimental pathology at Ancona will get the baton by the older one and lead the future with the same enthusiasm, love and commitment.

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The mitomiR/Bcl-2 axis affects mitochondrial function and autophagic vacuole formation in senescent endothelial cells

Cited by 30 publications

References 58 publications

Mitochondrial MiRNA in Cardiovascular Function and Disease

Mitochondrial MiRNA in Cardiovascular Function and Disease

The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract

The Experimental Pathology at Ancona: 50 Years of Exciting and Pioneering Research on Human Pathology

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