Extracellular adenine compounds within the cardiovascular system: Their source, metabolism and function

Soslau, Gerald

doi:10.1016/j.medidd.2020.100018

Cited by 5 publications

(2 citation statements)

References 219 publications

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“…Another important source of extracellular adenosine is the hydrolysis of adenine nucleotides by cell-surface ecto-nucleotidases ( Figure 1 ) [ 19 ]. Nucleotides are released to the extracellular compartment in response to cellular stress via lytic and non-lytic mechanisms [ 20 ]. Therefore, together with nucleotide-degrading ecto-enzymes and transmembrane adenosine transport, eADA plays an essential role in the regulation of extracellular adenosine concentration.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

et al. 2020

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Adenosine deaminase (ADA) is an enzyme of purine metabolism that irreversibly converts adenosine to inosine or 2′deoxyadenosine to 2′deoxyinosine. ADA is active both inside the cell and on the cell surface where it was found to interact with membrane proteins, such as CD26 and adenosine receptors, forming ecto-ADA (eADA). In addition to adenosine uptake, the activity of eADA is an essential mechanism that terminates adenosine signaling. This is particularly important in cardiovascular system, where adenosine protects against endothelial dysfunction, vascular inflammation, or thrombosis. Besides enzymatic function, ADA protein mediates cell-to-cell interactions involved in lymphocyte co-stimulation or endothelial activation. Furthermore, alteration in ADA activity was demonstrated in many cardiovascular pathologies such as atherosclerosis, myocardial ischemia-reperfusion injury, hypertension, thrombosis, or diabetes. Modulation of ADA activity could be an important therapeutic target. This work provides a systematic review of ADA activity and anchoring inhibitors as well as summarizes the perspectives of their therapeutic use in cardiovascular pathologies associated with increased activity of ADA.

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Section: Introductionmentioning

confidence: 99%

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

et al. 2020

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“…In extracellular space, nucleotides such as ATP, ADP, or UTP are released from the cells under many pathological stimuli and, via the P2 receptors, trigger pro-inflammatory and atherogenic effects [ 18 ]. In the cardiovascular system, extracellular nucleotides are deactivated by cell-surface ecto-nucleotidases that occur on different cell types, including cardiomyocytes, endothelium, or blood cells [ 19 ]. These include ecto-nucleoside triphosphate diphosphohydrolase-1 (CD39) and the following ecto-5′-nucleotidase (CD73) that are engaged in the hydrolysis of ATP or UTP via ADP (UDP) and AMP (UMP) to adenosine (uridine) [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Mitochondria Dysfunction in Dyslipidemic Mice

Braczko

Kutryb–Zajac

Jędrzejewska

et al. 2022

IJMS

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Dyslipidemia triggers many severe pathologies, including atherosclerosis and chronic inflammation. Several lines of evidence, including our studies, have suggested direct effects of dyslipidemia on cardiac energy metabolism, but details of these effects are not clear. This study aimed to investigate how mild dyslipidemia affects cardiac mitochondria function and vascular nucleotide metabolism. The analyses were performed in 3- and 6-month-old knock-out mice for low-density lipoprotein receptor (Ldlr−/−) and compared to wild-type C57Bl/6J mice (WT). Cardiac isolated mitochondria function was analyzed using Seahorse metabolic flux analyzer. The mechanical function of the heart was measured using echocardiography. The levels of fusion, fission, and mitochondrial biogenesis proteins were determined by ELISA kits, while the cardiac intracellular nucleotide concentration and vascular pattern of nucleotide metabolism ecto-enzymes were analyzed using reverse-phase high-performance liquid chromatography. We revealed the downregulation of mitochondrial complex I, together with a decreased activity of citrate synthase (CS), reduced levels of nuclear respiratory factor 1 and mitochondrial fission 1 protein, as well as lower intracellular adenosine and guanosine triphosphates’ pool in the hearts of 6-month Ldlr−/− mice vs. age-matched WT. The analysis of vascular ecto-enzyme pattern revealed decreased rate of extracellular adenosine monophosphate hydrolysis and increased ecto-adenosine deaminase activity (eADA) in 6-month Ldlr−/− vs. WT mice. No changes were observed in echocardiography parameters in both age groups of Ldlr−/− mice. Younger hyperlipidemic mice revealed no differences in cardiac mitochondria function, CS activity, intracellular nucleotides, mitochondrial biogenesis, and dynamics but exhibited minor changes in vascular eADA activity vs. WT. This study revealed that dysfunction of cardiac mitochondria develops during prolonged mild hyperlipidemia at the time point corresponding to the formation of early vascular alterations.

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Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache

Biringer

2023

Mol Cell Biochem

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Extracellular adenine compounds within the cardiovascular system: Their source, metabolism and function

Cited by 5 publications

References 219 publications

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Cardiac Mitochondria Dysfunction in Dyslipidemic Mice

Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache

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