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

Aging ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 2855-2873 ◽  
Author(s):  
Angelica Giuliani ◽  
Ilenia Cirilli ◽  
Francesco Prattichizzo ◽  
Emanuela Mensà ◽  
Gianluca Fulgenzi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Autophagic Vacuole ◽  
Vacuole Formation

Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells

2021 ◽  
Author(s):  
Anisha D'Souza ◽  
Amelia Burch ◽  
Kandarp M. Dave ◽  
Aravind Sreeram ◽  
Michael J. Reynolds ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Brain Endothelial Cells

Trans, trans-2,4-decadienal Induces Endothelial Cells Injury by Impairing Mitochondrial Function and Suppressing Autophagy

2021 ◽  
Author(s):  
Yuanyuan Hu ◽  
Guanhua Zhao ◽  
Lei Qin ◽  
Zhenlong Yu ◽  
Min Zhang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Crucial Role ◽  
Cardiovascular Health ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial

Trans, trans-2,4-decadienal (tt-DDE), one of the major lipid peroxidation-derived aldehydes, has unique reactivity that is potentially toxic to human. Vascular endothelial cells play a crucial role in maintaining cardiovascular health....

Abstract 3640: Mitochondrial Uncoupling Protein 2 Facilitates Endothelial Cell Growth and Angiogenesis via Reduction of Mitochondrial Superoxide

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yukio Shimasaki ◽  
Kai Chen ◽  
John F Keaney
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Mitochondrial Function ◽  
Endothelial Cell Proliferation ◽  
Wild Type ◽  
Sprouting Angiogenesis ◽  
Mitochondrial Superoxide ◽  
Endothelial Cell Growth ◽  
Aortic Explants

Background: Growing evidence suggests that mitochondrial function contributes to cell phenotype. One important component of mitochondrial function is the membrane potential that is controlled, in part, by uncoupling proteins (UCPs). Based on our previous data, the UCP2 is predominantly expressed in cultured endothelial cells. Therefore, we sought to examine the role of UCP2 in endothelial cell growth and angiogenesis. Methods and Results: Murine lung endothelial cells (MLECs) were isolated from UCP2-null and wild-type mice. UCP2-null cells were found less proliferative than wild-type cells (P<0.02, UCP2-null cells vs. wild-type cells, n=4). This defect of UCP2-null cells was rescued by UCP2 adenovirus transfection (19% increase, p<0.02 vs. LacZ adenovirus treated cells, n=3), and also rescued by transfection with manganese superoxide dismutase (MnSOD) adenovirus (53% increase, P<0.002 vs. LacZ adenovirus treated cells, n=3). We found a reciprocal relation such as no UCP2 expression and higher mitochondrial superoxide level in the MLECs (P<0.005, UCP2-null cells vs. wild-type cells, n=3), suggesting that mitochondrial superoxide may regulate endothelial cell growth. Then, we prepared murine aortic rings from UCP2-null and wild-type mice and embedded in rat tail collagen gel. The sprouting angiogenesis of UCP2-null explants was significantly less than wild-type explants (P<0.02, UCP2-null explants vs. wild-type explants, n=3– 4). Furthermore, MLECs from MnSOD-heterozygous mice showed less proliferation with lower expression of UCP2 protein and higher mitochondrial superoxide level compared to the MLECs from wild-type littermates (P<0.02, MnSOD-heterozygous cells vs. wild-type cells, n=4 – 8). We also observed less sprouting angiogenesis in MnSOD-heterozygous aortic explants than wild-type aortic explants (P<0.05, MnSOD-heterozygous explants vs. wild-type explants, n=3– 6). Conclusions: These data indicate that mitochondrial superoxide controls endothelial cell proliferation and angiogenesis, suggesting that mitochondrial metabolism modulates the endothelial cell growth and angiogenesis.

scholarly journals Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence

2008 ◽  
Vol 180 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Michael Schleicher ◽  
Benjamin R. Shepherd ◽  
Yajaira Suarez ◽  
Carlos Fernandez-Hernando ◽  
Jun Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Vascular System ◽  
Reactive Oxygen ◽  
Direct Consequence ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Prohibitin 1

Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells.

Abstract 327: Mitochondrial Functional Variation Contributes to Endothelial Cell Activation

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
David M Krzywanski ◽  
Bing Cheng ◽  
Xinggui Shen ◽  
Christopher Kevil
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Ethnic Groups ◽  
Mitochondrial Function ◽  
Cell Activation ◽  
Oxidant Stress ◽  
Oxygen Utilization ◽  
Endothelial Cell Activation ◽  
Inflammatory Conditions ◽  
Oxidant Production

Vascular oxidant stress contributes to endothelial dysfunction and plays a critical role in early stage cardiovascular disease (CVD) development. Changes in endothelial function due to oxidant stress may contribute to CVD initiation and progression through the development of a pro-inflammatory environment. Differences in mitochondrial function may contribute to this process and provide insight into why age of onset and clinical outcomes differ amongst individuals form distinct ethnic groups; but no reports demonstrate distinct mitochondrial functional parameters between normal cells. Consequently, we hypothesized that significant variations in normal mitochondrial function and oxidant production exist between endothelial cells from donors representing different ethnic groups. Aspects of mitochondrial oxygen utilization and oxidant production were assessed under basal and inflammatory conditions in human aortic endothelial cells (HAECs) isolated from African Americans (AA) and Caucasians (CA). Bioenergetic analysis indicates that compared to CA, AA HAEC utilized significantly less oxygen for ATP production, possess a lower maximal respiratory capacity, and have reduced electron leak. Significant differences in mitochondrial membrane potential, decreased expression of endothelial nitric oxide synthase, and increased levels of superoxide were also observed and AA HAEC supporting a pro-inflammatory phenotype. As a marker of endothelial cell activation, AA HAEC expressed increased levels of intercellular cell adhesion molecule-1 under both basal and inflammatory conditions that could be partially mitigated but treatment with the mitochondrially targeted antioxidant MitoTEMPO. These data demonstrate that fundamental differences exist in mitochondrial oxygen utilization and oxidant production between CA and AA HAEC and that these changes may affect endothelial cell activation. These findings are consistent with the hypothesis that differences in “normal” mitochondrial function amongst ethnic groups could influence individual susceptibility by contributing to vascular inflammation, providing important insights into the mechanisms that contribute human CVD development.

NCX‐4016, a nitric oxide‐releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial function

2002 ◽  
Vol 16 (12) ◽  
pp. 1645-1647 ◽  
Author(s):  
Stefano Fiorucci ◽  
Andrea Mencarelli ◽  
Roberta Mannucci ◽  
Eleonora Distrutti ◽  
Antonio Morelli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Nitric Oxide Releasing ◽  
Ncx 4016

scholarly journals Estrogen-Receptor-Mediated Protection of Cerebral Endothelial Cell Viability and Mitochondrial Function after Ischemic Insult in vitro

2009 ◽  
Vol 30 (3) ◽  
pp. 545-554 ◽  
Author(s):  
Jiabin Guo ◽  
Diana N Krause ◽  
James Horne ◽  
John H Weiss ◽  
Xuejun Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Endothelial Cell ◽  
Cell Viability ◽  
Mitochondrial Function ◽  
Protective Effects ◽  
Brain Endothelial Cells ◽  
Ischemic Insult ◽  
Mitochondrial Superoxide

Protective effects of estrogen against experimental stroke and neuronal ischemic insult are well-documented, but it is not known whether estrogen prevents ischemic injury to brain endothelium, a key component of the neurovascular unit. Increasing evidence indicates that estrogen exerts protective effects through mitochondrial mechanisms. We previously found 17β-estradiol (E2) to improve mitochondrial efficiency and reduce mitochondrial superoxide in brain blood vessels and endothelial cells. Thus we hypothesized E2 will preserve mitochondrial function and protect brain endothelial cells against ischemic damage. To test this, an in vitro ischemic model, oxygen-glucose deprivation (OGD)/reperfusion, was applied to immortalized mouse brain endothelial cells (bEnd.3). OGD/reperfusion-induced cell death was prevented by long-term (24, 48 h), but not short-term (0.5, 12 h), pretreatment with 10 nmol/L E2. Protective effects of E2 on endothelial cell viability were mimicked by an estrogen-receptor (ER) agonist selective for ERα (PPT), but not by one selective for ERβ (DPN). In addition, E2 significantly decreased mitochondrial superoxide and preserved mitochondrial membrane potential and ATP levels in early stages of OGD/reperfusion. All of the E2 effects were blocked by the ER antagonist, ICI-182,780. These findings indicate that E2 can preserve endothelial mitochondrial function and provide protection against ischemic injury through ER-mediated mechanisms.

Inhibition of apoptosis in pulmonary endothelial cells by altered pH, mitochondrial function, and ATP supply

2002 ◽  
Vol 283 (6) ◽  
pp. L1291-L1302 ◽  
Author(s):  
C. Terminella ◽  
K. Tollefson ◽  
J. Kroczynski ◽  
J. Pelli ◽  
M. Cutaia
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Dna Fragmentation ◽  
Mitochondrial Function ◽  
Atp Depletion ◽  
Apoptotic Cells ◽  
Caspase Activity ◽  
Human Pulmonary Artery ◽  
Induced Apoptosis ◽  
Atp Supply

We investigated the effect of altered extracellular pH, mitochondrial function, and ATP content on development of apoptosis in human pulmonary artery endothelial cells after treatment with staurosporine (STS). STS produced a concentration- and time-dependent increase in caspase-3 activity in pH 7.4 medium that reached a peak at 6 h. The increase in caspase activity was associated with significant DNA fragmentation. Fluorescent imaging of treated monolayers in pH 7.4 medium with Hoechst-33342-propidium iodide demonstrated a large percentage of apoptotic cells (∼40%) with no evidence of necrosis. Caspase activity, DNA fragmentation, and percentage of apoptotic cells were reduced after STS treatment in acidic media (pH 7.0 and 6.6). The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid-AM inhibited STS-induced apoptosis, whereas the rise in intracellular Ca2+ concentration in STS-treated cells in pH 7.4 medium was reduced in pH 7.0 medium. These results suggest that one mechanism for inhibitory effects of acidosis may be a pH-induced alteration in Ca2+ signaling. Treatment with STS in the presence of oligomycin (10 μM), an inhibitor of the mitochondrial F0F1-ATPase, in glucose-free media abolished caspase activation and DNA fragmentation in association with severe ATP depletion (∼2% of control cells). Imaging demonstrated a change in the mode of cell death from apoptosis to necrosis under these conditions. This change was linked to the level of ATP depletion, because STS treatment in the absence of glucose or the presence of oligomycin in media with glucose still leads to apoptosis in the presence of only moderate ATP depletion. These results demonstrate that pH, mitochondrial function, and ATP supply are important variables that regulate STS-induced apoptosis in human pulmonary artery endothelial cells.

scholarly journals How AMPK and PKA Interplay to Regulate Mitochondrial Function and Survival in Models of Ischemia and Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jingdian Zhang ◽  
Yumeng Wang ◽  
Xiaofeng Liu ◽  
Ruben K. Dagda ◽  
Ying Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Protein Kinase ◽  
Cell Survival ◽  
Mitochondrial Function ◽  
Molecular Mechanisms ◽  
Temporal Dynamics ◽  
Protein Translation ◽  
Conservation Of Energy

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved, redox-activated master regulator of cell metabolism. In the presence of oxidative stress, AMPK promotes cytoprotection by enhancing the conservation of energy by suppressing protein translation and by stimulating autophagy. AMPK interplays with protein kinase A (PKA) to regulate oxidative stress, mitochondrial function, and cell survival. AMPK and dual-specificity A-kinase anchoring protein 1 (D-AKAP1), a mitochondrial-directed scaffold of PKA, interact to regulate mitochondrial function and oxidative stress in cardiac and endothelial cells. Ischemia and diabetes, a chronic disease that increases the onset of cardiovascular diseases, suppress the cardioprotective effects of AMPK and PKA. Here, we review the molecular mechanisms by which AMPK and D-AKAP1/PKA interplay to regulate mitochondrial function, oxidative stress, and signaling pathways that prime endothelial cells, cardiac cells, and neurons for cytoprotection against oxidative stress. We discuss recent literature showing how temporal dynamics and localization of activated AMPK and PKA holoenzymes play a crucial role in governing cellular bioenergetics and cell survival in models of ischemia, cardiovascular diseases, and diabetes. Finally, we propose therapeutic strategies that tout localized PKA and AMPK signaling to reverse mitochondrial dysfunction, oxidative stress, and death of neurons and cardiac and endothelial cells during ischemia and diabetes.

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