Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells

Yang, Mingming; Dart, Caroline; Kamishima, Tomoko; Quayle, J. M.

doi:10.7717/peerj.10344

Cited by 5 publications

(3 citation statements)

References 72 publications

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“…Our results on ATP, ADP, AMP, and energy charge levels changes in testicular cells of rats with juvenile-onset metabolic syndrome and administration of metformin or its combination with MV or PQ are fully consistent with the data of other authors, established the existence of a clear dependence of the content of ATP and ADP on the concentration of glucose in the blood [49]. Such changes in the content of ATP, ADP, and AMP with MS may be caused by disturbances in the activity of adenosine deaminase, similar to those observed with diabetes [50].…”

Section: Discussionsupporting

confidence: 93%

Effects of Metformin and Preparations With Pleiotropic Effects on Testicular Biochemical Indices of Rats With Juvenile-Onset Metabolic Syndrome

Bondarenko,

Shayakhmetova,

Tkachenko

et al. 2023

Innov Biosyst Bioeng

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Background. Metabolic syndrome (MS) is a complex of disorders characterized by abdominal obesity, insulin resistance and glucose tolerance, arterial hypertension, and all types of metabolic disorders. Taking into account the wide range of symptoms accompanying MS, the use of preparations with pleiotropic effects on metabolic processes in the body could be promising for its treatment. Objective. The aim of this study is comparative estimation of metformin or its combination with vitamins' complex or liposomal preparation treatment effects on DNA, RNA, histones, ATP, ADP, AMP contents, and DNA fragmentation processes in testes of rats with MS induced in juvenile age. Methods. MS model was induced by full replacement of drinking water with 10% fructose solution in Wistar male rats of 21–23 days age (50–70 g). DNA, RNA, histones, ATP, ADP, AMP contents, and DNA fragmentation processes investigations were carried out after 60 days of MS modeling and metformin or its combination with vitamins' complex or liposomal preparation treatment. Results. In experiments with pubertal rats with MS and metformin or its combination vitamins' complex or liposomal preparation treatment, we established partially corrective effects of these medications for DNA, RNA, histones, ATP, ADP, AMP contents, and DNA fragmentation processes changes caused by MS development. Conclusions. A comparative analysis of the studied preparations' effects under MS simulation in the juvenile age showed that none of these drugs was able to completely normalize the disorders in studied indicators caused by MS. However, both combinations of metformin with vitamins' complex or liposomal preparation were still more effective in these negative changes' correction then metformin itself. Metformin with vitamins' complex caused a more pronounced influence on the processes of DNA fragmentation, the levels of adenyl nucleotides, and the energy charge of rat testicular cells, while the corrective effect of metformin with liposomal preparation was more noticeable with respect to the content of chromatin components.

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Section: Discussionsupporting

confidence: 93%

Effects of Metformin and Preparations With Pleiotropic Effects on Testicular Biochemical Indices of Rats With Juvenile-Onset Metabolic Syndrome

Bondarenko,

Shayakhmetova,

Tkachenko

et al. 2023

Innov Biosyst Bioeng

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“…The mitochondria of the vascular smooth muscle cells (VSMCs) and PAECs, as in any other cells, are responsible for the synthesis of ATP, the key energetic molecule, thus a strict control of metabolism is exerted by these double-membrane-bound organelles [97]. In addition, mitochondria take an important place in the production and regulation of ROS, Ca 2+ signaling, metabolism of glucose and FA, and apoptosis.…”

Section: Mitochondria In Vascular Remodeling During Phmentioning

confidence: 99%

Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension

et al. 2022

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Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca2+ signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron–sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca2+ levels. Mitochondrial ROS and Ca2+ can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. Evidence suggests that increased mitochondrial ROS and Ca2+ signaling leads to abnormal synthesis of ketones, which play a critical role in the development of PH. In this review, we discuss some of the recent findings on the important interactive role and molecular mechanisms of mitochondrial ROS and Ca2+ in the development and progression of PH. We also address the contributions of NF-κB-dependent inflammatory responses and ketone-mediated oxidative stress due to abnormal regulation of mitochondrial ROS and Ca2+ signaling in PH.

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“…The heart operates exclusively under aerobic metabolism and three factors, heart rate, contractility, and ventricular wall tension, require myocardial mitochondria for maintaining sufficient O 2 to sustain oxidative phosphorylation. Hypoxia causes the opening of the K ATP channel due to a decline in the ATP:ADP ratio, which couples cellular metabolism to excitability to prevent action potential generation and cell contraction, ultimately leading to coronary artery smooth muscle cell hyperpolarization and the closure of voltage-dependent Ca 2+ channels and relaxation ( Yang et al, 2020a ). Vascular K ATP channels supporting skeletal muscle convective and diffusive O 2 transport and oxidative phosphorylation sustain submaximal exercise tolerance; conversely, K ATP channel inhibitors may exacerbate exercise intolerance in healthy rats ( Colburn et al, 2020 ).…”

Section: Regulation Of K Atp Channels By Small Act...mentioning

confidence: 99%

Functional Regulation of KATP Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

et al. 2022

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ATP-sensitive potassium channels (KATP channels) play pivotal roles in excitable cells and link cellular metabolism with membrane excitability. The action potential converts electricity into dynamics by ion channel-mediated ion exchange to generate systole, involved in every heartbeat. Activation of the KATP channel repolarizes the membrane potential and decreases early afterdepolarization (EAD)-mediated arrhythmias. KATP channels in cardiomyocytes have less function under physiological conditions but they open during severe and prolonged anoxia due to a reduced ATP/ADP ratio, lessening cellular excitability and thus preventing action potential generation and cell contraction. Small active molecules activate and enhance the opening of the KATP channel, which induces the repolarization of the membrane and decreases the occurrence of malignant arrhythmia. Accumulated evidence indicates that mutation of KATP channels deteriorates the regulatory roles in mutation-related diseases. However, patients with mutations in KATP channels still have no efficient treatment. Hence, in this study, we describe the role of KATP channels and subunits in angiocardiopathy, summarize the mutations of the KATP channels and the functional regulation of small active molecules in KATP channels, elucidate the potential mechanisms of mutant KATP channels and provide insight into clinical therapeutic strategies.

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Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells

Cited by 5 publications

References 72 publications

Effects of Metformin and Preparations With Pleiotropic Effects on Testicular Biochemical Indices of Rats With Juvenile-Onset Metabolic Syndrome

Effects of Metformin and Preparations With Pleiotropic Effects on Testicular Biochemical Indices of Rats With Juvenile-Onset Metabolic Syndrome

Important Functions and Molecular Mechanisms of Mitochondrial Redox Signaling in Pulmonary Hypertension

Functional Regulation of KATP Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

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