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Frontiers in Immunology 2022Heart transplantation remains the optimal treatment option for patients with end-stage heart disease. Growing evidence demonstrates that purinergic signals mediated by... (Review)
Review
Heart transplantation remains the optimal treatment option for patients with end-stage heart disease. Growing evidence demonstrates that purinergic signals mediated by purine nucleotides and nucleosides play vital roles in heart transplantation, especially in the era of ischemia-reperfusion injury (IRI) and allograft rejection. Purinergic signaling consists of extracellular nucleotides and nucleosides, ecto-enzymes, and cell surface receptors; it participates in the regulation of many physiological and pathological processes. During transplantation, excess adenosine triphosphate (ATP) levels are released from damaged cells, and driver detrimental inflammatory responses largely purinergic P2 receptors. Ecto-nucleosidases sequentially dephosphorylate extracellular ATP to ADP, AMP, and finally adenosine. Adenosine exerts a cardioprotective effect by its anti-inflammatory, antiplatelet, and vasodilation properties. This review focused on the role of purinergic signaling in IRI and rejection after heart transplantation, as well as the clinical applications and prospects of purinergic signaling.
Topics: Adenosine; Adenosine Triphosphate; Heart Transplantation; Humans; Nucleosides; Nucleotides
PubMed: 35529844
DOI: 10.3389/fimmu.2022.826943 -
Current Heart Failure Reports Apr 2022We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate... (Review)
Review
PURPOSE OF REVIEW
We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate utilization for adenosine triphosphate (ATP) production.
RECENT FINDINGS
Mitochondria-targeted therapies have been tested in animal models of and humans with heart failure (HF). Cardiac benefits of sodium/glucose cotransporter 2 inhibitors might be partly explained by their effects on ion handling and metabolism of cardiac myocytes. The large energy requirements of the heart are met by oxidative phosphorylation in mitochondria, which is tightly regulated by the turnover of ATP that fuels cardiac contraction and relaxation. In heart failure (HF), this mechano-energetic coupling is disrupted, leading to bioenergetic mismatch and production of ROS that drive the progression of cardiac dysfunction. Furthermore, HF is accompanied by changes in substrate uptake and oxidation that are considered detrimental for mitochondrial oxidative metabolism and negatively affect cardiac efficiency. Mitochondria lie at the crossroads of metabolic and energetic dysfunction in HF and represent ideal therapeutic targets.
Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Heart Failure; Humans; Mitochondria, Heart; Myocytes, Cardiac; Oxidative Stress; Reactive Oxygen Species
PubMed: 35147851
DOI: 10.1007/s11897-022-00539-0 -
International Journal of Molecular... May 2023Since its inception by the late Geoffrey Burnstock in the early 1970s [...].
Since its inception by the late Geoffrey Burnstock in the early 1970s [...].
Topics: Receptors, Purinergic; Signal Transduction; Biological Phenomena; Adenosine Triphosphate
PubMed: 37298149
DOI: 10.3390/ijms24119196 -
Biological Chemistry Nov 2020A main function of bacterial metabolism is to supply biomass building blocks and energy for growth. This seems to imply that metabolism is idle in non-growing bacteria.... (Review)
Review
A main function of bacterial metabolism is to supply biomass building blocks and energy for growth. This seems to imply that metabolism is idle in non-growing bacteria. But how relevant is metabolism for the physiology of non-growing bacteria and how active is their metabolism? Here, we reviewed literature describing metabolism of non-growing bacteria in their natural environment, as well as in biotechnological and medical applications. We found that metabolism does play an important role during dormancy and that especially the demand for ATP determines metabolic activity of non-growing bacteria.
Topics: Adenosine Triphosphate; Bacteria; Biotechnology
PubMed: 32845858
DOI: 10.1515/hsz-2020-0201 -
Cells Feb 2023During transcription, DNA replication and repair, chromatin structure is constantly modified to reveal specific genetic regions and allow access to DNA-interacting... (Review)
Review
During transcription, DNA replication and repair, chromatin structure is constantly modified to reveal specific genetic regions and allow access to DNA-interacting enzymes. ATP-dependent chromatin remodelling complexes use the energy of ATP hydrolysis to modify chromatin architecture by repositioning and rearranging nucleosomes. These complexes are defined by a conserved SNF2-like, catalytic ATPase subunit and are divided into four families: CHD, SWI/SNF, ISWI and INO80. ATP-dependent chromatin remodellers are crucial in regulating development and stem cell biology in numerous organs, including the inner ear. In addition, mutations in genes coding for proteins that are part of chromatin remodellers have been implicated in numerous cases of neurosensory deafness. In this review, we describe the composition, structure and functional activity of these complexes and discuss how they contribute to hearing and neurosensory deafness.
Topics: Humans; Chromatin; Transcription Factors; Chromatin Assembly and Disassembly; Adenosine Triphosphate; Hearing Loss, Sensorineural
PubMed: 36831199
DOI: 10.3390/cells12040532 -
International Journal of Molecular... Nov 2022Mitochondria are considered the 'powerhouses' of cells, generating the essential energy in the form of adenosine triphosphate that they need for their energy demands.... (Review)
Review
Mitochondria are considered the 'powerhouses' of cells, generating the essential energy in the form of adenosine triphosphate that they need for their energy demands. Nevertheless, their function is easily adaptable as regards the energy demands and the availability of chemical substrates. This allows cells to buffer sudden changes and reassure cellular metabolism, growth or survival. Currently, humans have different dietary habits, which provide several stimuli to the cell. According to the energy substrate availability due to the diet quality and diet temporality, mitochondrial physiology is greatly affected. The present review article aimed to collect all the available information that has been published to date concerning the impact of five different popular diets (high‑fat diet, ketogenic diet, fasting, caloric restriction diet and the Mediterranean diet) on specific mitochondrial physiological aspects, such as function, biogenesis, mitophagy and mitochondrial fission/fusion.
Topics: Adenosine Triphosphate; Diet, High-Fat; Humans; Mitochondria; Mitochondrial Dynamics; Mitophagy
PubMed: 36129147
DOI: 10.3892/ijmm.2022.5191 -
ESC Heart Failure Oct 2023Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF.
METHODS AND RESULTS
The DoPING-HFpEF trial was a phase II single-centre, double-blind, placebo-controlled, randomized cross-over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2-week wash-out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m ); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI -2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6-min walking distance (mean change of -6 [95% CI -18, 7] m vs. -5 [95% CI -22, 22] m, respectively, P = 0.93), N-terminal pro-B-type natriuretic peptide (5 (-156, 166) ng/L vs. -13 (-172, 147) ng/L, P = 0.70), overall quality-of-life (KCCQ and EQ-5D-5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters.
CONCLUSIONS
Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.
Topics: Humans; Male; Female; Aged; Heart Failure; Trimetazidine; Phosphocreatine; Cross-Over Studies; Stroke Volume; Adenosine Triphosphate
PubMed: 37530098
DOI: 10.1002/ehf2.14418 -
Molecules (Basel, Switzerland) Mar 2022Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP... (Review)
Review
Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP acts at plasma membrane P2 receptors (P2Rs). The levels of extracellular ATP (eATP) are set by both passive and active release mechanisms and degradation processes. Under physiological conditions, eATP concentration is in the low nanomolar range but can rise to tens or even hundreds of micromoles/L at inflammatory sites. A dysregulated eATP homeostasis is a pathogenic factor in several chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). T2DM is characterized by peripheral insulin resistance and impairment of insulin production from pancreatic β-cells in a landscape of systemic inflammation. Although various hypoglycemic drugs are currently available, an effective treatment for T2DM and its complications is not available. However, counteracting systemic inflammation is anticipated to be beneficial. The postulated eATP increase in T2DM is understood to be a driver of inflammation via P2X7 receptor (P2X7R) activation and the release of inflammatory cytokines. Furthermore, P2X7R stimulation is thought to trigger apoptosis of pancreatic β-cells, thus further aggravating hyperglycemia. Targeting eATP and the P2X7R might be an appealing novel approach to T2DM therapy.
Topics: Adenosine Triphosphate; Cytokines; Diabetes Mellitus, Type 2; Humans; Inflammation; Signal Transduction
PubMed: 35335211
DOI: 10.3390/molecules27061838 -
Protein Science : a Publication of the... Jul 2021Proteins function in the crowded cellular environments with high salt concentrations, thus facing tremendous challenges of misfolding/aggregation which represents a... (Review)
Review
Proteins function in the crowded cellular environments with high salt concentrations, thus facing tremendous challenges of misfolding/aggregation which represents a pathological hallmark of aging and an increasing spectrum of human diseases. Recently, intrinsically disordered regions (IDRs) were recognized to drive liquid-liquid phase separation (LLPS), a common principle for organizing cellular membraneless organelles (MLOs). ATP, the universal energy currency for all living cells, mysteriously has concentrations of 2-12 mM, much higher than required for its previously-known functions. Only recently, ATP was decoded to behave as a biological hydrotrope to inhibit protein LLPS and aggregation at mM. We further revealed that ATP also acts as a bivalent binder, which not only biphasically modulates LLPS driven by IDRs of human and viral proteins, but also bind to the conserved nucleic-acid-binding surfaces of the folded proteins. Most unexpectedly, ATP appears to act as a hydration mediator to antagonize the crowding-induced destabilization as well as to enhance folding of proteins without significant binding. Here, this review focuses on summarizing the results of these biophysical studies and discussing their implications in an evolutionary context. By linking triphosphate with unique hydration property to adenosine, ATP appears to couple the ability for establishing hydrophobic, π-π, π-cation and electrostatic interactions to the capacity in mediating hydration of proteins, which is at the heart of folding, dynamics, stability, phase separation and aggregation. Consequently, ATP acquired a category of functions at ~mM to energy-independently control protein homeostasis with diverse mechanisms, thus implying a link between cellular ATP concentrations and protein-aggregation diseases.
Topics: Adenosine Triphosphate; Animals; Homeostasis; Humans; Protein Domains; Protein Folding; Proteostasis
PubMed: 33829608
DOI: 10.1002/pro.4079 -
Aging Sep 2018
Topics: Adenosine Triphosphate; Aging; Humans; Low-Level Light Therapy
PubMed: 30219804
DOI: 10.18632/aging.101556