scholarly journals Reactive Oxygen Species and Endothelial Ca2+ Signaling: Brothers in Arms or Partners in Crime?

2021 ◽  
Vol 22 (18) ◽  
pp. 9821
Author(s):  
Sharon Negri ◽  
Pawan Faris ◽  
Francesco Moccia
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Pulmonary Artery Hypertension ◽  
Ros Generation ◽  
Oxygen Species ◽  
Cell Functions

An increase in intracellular Ca2+ concentration ([Ca2+]i) controls virtually all endothelial cell functions and is, therefore, crucial to maintain cardiovascular homeostasis. An aberrant elevation in endothelial can indeed lead to severe cardiovascular disorders. Likewise, moderate amounts of reactive oxygen species (ROS) induce intracellular Ca2+ signals to regulate vascular functions, while excessive ROS production may exploit dysregulated Ca2+ dynamics to induce endothelial injury. Herein, we survey how ROS induce endothelial Ca2+ signals to regulate vascular functions and, vice versa, how aberrant ROS generation may exploit the Ca2+ handling machinery to promote endothelial dysfunction. ROS elicit endothelial Ca2+ signals by regulating inositol-1,4,5-trisphosphate receptors, sarco-endoplasmic reticulum Ca2+-ATPase 2B, two-pore channels, store-operated Ca2+ entry (SOCE), and multiple isoforms of transient receptor potential (TRP) channels. ROS-induced endothelial Ca2+ signals regulate endothelial permeability, angiogenesis, and generation of vasorelaxing mediators and can be exploited to induce therapeutic angiogenesis, rescue neurovascular coupling, and induce cancer regression. However, an increase in endothelial [Ca2+]i induced by aberrant ROS formation may result in endothelial dysfunction, inflammatory diseases, metabolic disorders, and pulmonary artery hypertension. This information could pave the way to design alternative treatments to interfere with the life-threatening interconnection between endothelial ROS and Ca2+ signaling under multiple pathological conditions.

scholarly journals Reactive Oxygen Species Downregulate Transient Receptor Potential Melastatin 6 Expression Mediated by the Elevation of miR-24-3p in Renal Tubular Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1893
Author(s):  
Chieko Hirota ◽  
Yui Takashina ◽  
Yuta Yoshino ◽  
Hajime Hasegawa ◽  
Ema Okamoto ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Transient Receptor Potential ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Fluorescence Measurement ◽  
Oxygen Species ◽  
Green Fluorescence ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Renal Tubular

Background: A low level of serum magnesium ion (Mg2+) is associated with type 2 diabetes mellitus (T2D). However, the molecular mechanism of Mg2+ deficiency has not been fully clarified. The current study sought to assesses the effect of reactive oxygen species on the expression of Mg2+ channels and miRNA. Methods: The expression of Mg2+ channels and miRNA were examined by real-time polymerase chain reaction. Intracellular Mg2+ concentration was measured by Magnesium Green fluorescence measurement. Results: The mRNA level of transient receptor potential melastatin 6 (TRPM6), which functions as Mg2+ influx channel in the distal convoluted tubule (DCT) of the kidney, was decreased by glycated albumin (GA), but not by insulin in rat renal tubule-derived NRK-52E cells. The mRNA levels of TRPM7, a homologue of TRPM6, and CNNM2, a Mg2+ efflux transporter located at the basolateral membrane of DCT, were changed by neither GA nor insulin. The generation of reactive oxygen species (ROS) was increased by GA. Hydrogen peroxide (H2O2) dose-dependently decreased TRPM6 mRNA, but it inversely increased the reporter activity of TRPM6. H2O2 accelerated the degradation of TRPM6 mRNA in actinomycin D assay without affecting TRPM7 and CNNM2 mRNA expressions. Nine miRNAs were considered as candidates for the regulator of stability of TRPM6 mRNA. Among them, miR-24-3p expression was increased by H2O2. The H2O2-induced reduction of TRPM6 mRNA was rescued by miR-24-3p siRNA. Magnesium Green fluorescence measurement showed that Mg2+ influx is suppressed by H2O2, which was rescued by an antioxidant and miR-24-3p siRNA. Conclusions: We suggest that GA decreases TRPM6 expression mediated by the elevation of ROS and miR-24-3p in renal tubular epithelial cells of T2D.

scholarly journals Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species

2021 ◽  
Vol 22 (14) ◽  
pp. 7589
Author(s):  
Anberitha T. Matthews ◽  
Hitesh Soni ◽  
Katherine E. Robinson-Freeman ◽  
Theresa A. John ◽  
Randal K. Buddington ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Transient Receptor Potential ◽  
Mesangial Cell ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Oxygen Species ◽  
Glomerular Mesangial Cell ◽  
Trpc6 Channel ◽  
Fetal Pig

Doxorubicin (DOX), a category D pregnancy drug, is a chemotherapeutic agent that has been shown in animal studies to induce fetal toxicity, including renal abnormalities. Upregulation of the transient receptor potential cation (TRPC) 6 channel is involved in DOX-induced podocyte apoptosis. We have previously reported that TRPC6-mediated Ca2+ signaling promotes neonatal glomerular mesangial cell (GMC) death. However, it is unknown whether DOX alters mesangial TRPC expression or viability in the fetus. In this study, cell growth was tracked in control and DOX-treated primary GMCs derived from fetal pigs. Live-cell imaging demonstrated that exposure to DOX inhibited the proliferation of fetal pig GMCs and induced cell death. DOX did not alter the TRPC3 expression levels. By contrast, TRPC6 protein expression in the cells was markedly reduced by DOX. DOX treatment also attenuated the TRPC6-mediated intracellular Ca2+ elevation. DOX stimulated mitochondrial reactive oxygen species (mtROS) generation and mitophagy by the GMCs. The DOX-induced mtROS generation and apoptosis were reversed by the mitochondria-targeted antioxidant mitoquinone. These data suggest that DOX-induced fetal pig GMC apoptosis is independent of TRPC6 channel upregulation but requires mtROS production. The mtROS-dependent GMC death may contribute to DOX-induced fetal nephrotoxicity when administered prenatally.

scholarly journals Recent advances in oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction

2017 ◽  
Vol 123 (6) ◽  
pp. 1647-1656 ◽  
Author(s):  
Ievgen Strielkov ◽  
Oleg Pak ◽  
Natasha Sommer ◽  
Norbert Weissmann
Keyword(s):  
Reactive Oxygen Species ◽  
Transient Receptor Potential ◽  
Oxygen Sensing ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Complex Iii ◽  
Oxygen Species ◽  
Pulmonary Vasoconstriction ◽  
Transient Receptor

Hypoxic pulmonary vasoconstriction (HPV) is a physiological reaction, which adapts lung perfusion to regional ventilation and optimizes gas exchange. Impaired HPV may cause systemic hypoxemia, while generalized HPV contributes to the development of pulmonary hypertension. The triggering mechanisms underlying HPV are still not fully elucidated. Several hypotheses are currently under debate, including a possible decrease as well as an increase in reactive oxygen species as a triggering event. Recent findings suggest an increase in the production of reactive oxygen species in pulmonary artery smooth muscle cells by complex III of the mitochondrial electron transport chain and occurrence of oxygen sensing at complex IV. Other essential components are voltage-dependent potassium and possibly L-type, transient receptor potential channel 6, and transient receptor potential vanilloid 4 channels. The release of arachidonic acid metabolites appears also to be involved in HPV regulation. Further investigation of the HPV mechanisms will facilitate the development of novel therapeutic strategies for the treatment of HPV-related disorders.

Abstract 500: Reactive Oxygen Species and Insufficiency of Nitric Oxide Mediate Enhanced Microvascular Contractility and Impaired Endothelium Dependent Relaxation in Mice With Renal Failure

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Cheng Wang ◽  
Christopher S Wilcox
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Sham Operation ◽  
Oxygen Species ◽  
Channel Dependent ◽  
Microscopy Data ◽  
Endothelium Dependent Relaxation

Background: Cardiovascular disease (CVD) is common and major cause of death and disability in chronic kidney disease (CKD). Since CVD starts with endothelial dysfunction, we tested the hypothesis that reactive oxygen species (ROS) and insufficient nitric oxide (NO) contributed to microvascular contractility and endothelial dysfunction in C57BL/6 mice with normotensive reduced renal mass (RRM) 5/6 nephrectomy, a model of progressive CKD. Methods and Results: Mesenteric arterioles (MAs) were isolated from mice 3 months after sham-operation (Sham) or RRM (n=6/group) and were mounted on Mulvany-Halperin wire myograph, preconstricted with norepinephrine and relaxed with acetylcholine (ACh) for: endothelium-dependent relaxation (EDR); endothelium-dependent relaxation factor (EDRF; NOS-dependent relaxation); endothelium-dependent hyperpolarizing factor (EDHF; K + -channel dependent relaxation) and endothelium-independent relaxation (EIR; sodium nitroprusside). Contractions were tested to endothelium-dependent contracting factor (EDCF; ACh-induced contraction with blocked relaxation pathways); phenylephrine (PE); U-46,619 (thromboxane-prostanoid receptor agonist) and endothelin-1 (ET-1). NO activity (DAF-FM fluorescence) and ROS generation (tempo-9-AC fluorescence) were measured by fluorescence microscopy. Data are mean ±SEM. The MAs from RRM mice had diminished EDR (54 ±5 vs. 77±3%; P<0.01) and EDRF (13±5 vs. 27±4%; P<0.01) with reduced NO activity (0.18 ± 0.05 vs. 0.36± 0.04 ΔUnits; P<0.05), but unchanged EDHF (30±4 vs. 38±4%; NS). These vessels from RRM mice developed an EDCF (14±1 vs. 8±1%; P<0.05) and ACh-induced increased in ROS (0.17±0.03 vs. 0.06±0.02 ΔUnits; P<0.05). Contractile responses were enhanced to U-46,619 (107±4 vs. 87±6, P<0.05) and ET-1 (108±7 vs. 89±4, P<0.05), but not to PE (87±6 vs. 77±8%, NS). Conclusion: mice with RRM developed defective microvascular EDR, EDRF with reduced NO activity and enhanced new ACh-induced EDCF, contractilities to thromboxane and endothelin with increased ROS generation. These microvascular disturbances may contribute to the later development of thrombosis, vascular remodeling and dysfunction in patients with CKD. *D. Wang and C.Wang: Equal contribution

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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