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The Veterinary Clinics of North... Sep 2020Feline infectious peritonitis (FIP) is a mysterious and lethal disease of cats. The causative agent, feline coronavirus (FCoV), is ubiquitous in most feline populations,... (Review)
Review
Feline infectious peritonitis (FIP) is a mysterious and lethal disease of cats. The causative agent, feline coronavirus (FCoV), is ubiquitous in most feline populations, yet the disease is sporadic in nature. Mutations in the infecting virus combined with an inappropriate immune response to the FCoV contribute to the development of FIP. Diagnosis can be challenging because signs may be vague, clinical pathology parameters are nonspecific, and the gold standard for diagnosis is invasive: histopathology of affected tissue. This article discusses the developments in the understanding of this disease as well as the progress in diagnosis and treatment.
Topics: Adenosine Triphosphate; Animals; Antiviral Agents; Cats; Coronavirus, Feline; Feline Infectious Peritonitis; Genetic Predisposition to Disease; Pyrrolidines; Sulfonic Acids
PubMed: 32563530
DOI: 10.1016/j.cvsm.2020.05.002 -
Targeting OXPHOS and the electron transport chain in cancer; Molecular and therapeutic implications.Seminars in Cancer Biology Nov 2022Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought... (Review)
Review
Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges.
Topics: Humans; Oxidative Phosphorylation; Electron Transport; Glycolysis; Neoplasms; Adenosine Triphosphate
PubMed: 35122973
DOI: 10.1016/j.semcancer.2022.02.002 -
Archives of Biochemistry and Biophysics Jul 2019
Topics: Adenosine Triphosphate; Calcium; Mitochondria; Muscles; Reactive Oxygen Species; Signal Transduction
PubMed: 31112707
DOI: 10.1016/j.abb.2019.05.015 -
Frontiers in Endocrinology 2022Adenosine triphosphate (ATP) serves as the essential source of cellular energy. Over the last two decades, however, ATP has also attracted increasing interest as an... (Review)
Review
Adenosine triphosphate (ATP) serves as the essential source of cellular energy. Over the last two decades, however, ATP has also attracted increasing interest as an extracellular signal that activates purinergic plasma membrane receptors of the P2 family. P2 receptors are divided into two types: ATP-gated nonselective cation channels (P2X) and G protein-coupled receptors (P2Y), the latter being activated by a broad range of purine and pyrimidine nucleotides (ATP, ADP, UTP, and UDP, among others). Purinergic signaling mechanisms are involved in numerous physiological events and pathophysiological conditions. Here, we address the growing body of evidence implicating purinergic signaling in male reproductive system functions. The life-long generation of fertile male germ cells is a highly complex, yet mechanistically poorly understood process. Given the relatively sparse innervation of the testis, spermatogenesis relies on both endocrine control and multi-directional paracrine communication. Therefore, a detailed understanding of such paracrine messengers, including ATP, is crucial to gain mechanistic insight into male reproduction..
Topics: Adenosine Triphosphate; Endocrine System; Humans; Male; Receptors, Purinergic; Signal Transduction; Spermatogenesis
PubMed: 35480481
DOI: 10.3389/fendo.2022.867011 -
Nature Aug 2023Uncoupling protein 1 (UCP1) conducts protons through the inner mitochondrial membrane to uncouple mitochondrial respiration from ATP production, thereby converting the...
Uncoupling protein 1 (UCP1) conducts protons through the inner mitochondrial membrane to uncouple mitochondrial respiration from ATP production, thereby converting the electrochemical gradient of protons into heat. The activity of UCP1 is activated by endogenous fatty acids and synthetic small molecules, such as 2,4-dinitrophenol (DNP), and is inhibited by purine nucleotides, such as ATP. However, the mechanism by which UCP1 binds to these ligands remains unknown. Here we present the structures of human UCP1 in the nucleotide-free state, the DNP-bound state and the ATP-bound state. The structures show that the central cavity of UCP1 is open to the cytosolic side. DNP binds inside the cavity, making contact with transmembrane helix 2 (TM2) and TM6. ATP binds in the same cavity and induces conformational changes in TM2, together with the inward bending of TM1, TM4, TM5 and TM6 of UCP1, resulting in a more compact structure of UCP1. The binding site of ATP overlaps with that of DNP, suggesting that ATP competitively blocks the functional engagement of DNP, resulting in the inhibition of the proton-conducting activity of UCP1.
Topics: Humans; Adenosine Triphosphate; Protons; Uncoupling Protein 1; Fatty Acids; 2,4-Dinitrophenol; Protein Conformation; Cell Membrane; Cytosol
PubMed: 37336486
DOI: 10.1038/s41586-023-06332-w -
The EMBO Journal Jul 2021While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor... (Review)
Review
While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and cell types involved, but also on the activation status of cis- and trans-regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
Topics: Adenosine Triphosphate; Animals; Humans; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 34121201
DOI: 10.15252/embj.2021108130 -
Pharmacological Research Dec 2020This review discusses the evidence supporting a role for ATP signaling (operated by PX and PY receptors) and adenosine signaling (mainly operated by A and A receptors)... (Review)
Review
This review discusses the evidence supporting a role for ATP signaling (operated by PX and PY receptors) and adenosine signaling (mainly operated by A and A receptors) in the crosstalk between neurons, astrocytes, microglia and oligodendrocytes. An initial emphasis will be given to the cooperation between adenosine receptors to sharpen information salience encoding across synapses. The interplay between ATP and adenosine signaling in the communication between astrocytes and neurons will then be presented in context of the integrative properties of the astrocytic syncytium, allowing to implement heterosynaptic depression processes in neuronal networks. The process of microglia 'activation' and its control by astrocytes and neurons will then be analyzed under the perspective of an interplay between different P receptors and adenosine A receptors. In spite of these indications of a prominent role of purinergic signaling in the bidirectional communication between neurons and glia, its therapeutical exploitation still awaits obtaining an integrated view of the spatio-temporal action of ATP signaling and adenosine signaling, clearly distinguishing the involvement of both purinergic signaling systems in the regulation of physiological processes and in the control of pathogenic-like responses upon brain dysfunction or damage.
Topics: Adenosine Triphosphate; Animals; Cell Communication; Humans; Neuroglia; Neurons; Signal Transduction
PubMed: 33080321
DOI: 10.1016/j.phrs.2020.105253 -
Cold Spring Harbor Perspectives in... Mar 2021
Review
Topics: Adenosine Triphosphate; Archaea; Calcium; Citric Acid Cycle; Glucose; Glycolysis; Homeostasis; Mitochondria; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Proteobacteria; Reactive Oxygen Species; Symbiosis
PubMed: 33649187
DOI: 10.1101/cshperspect.a040543 -
Journal of Cellular Physiology Jan 2022Purinergic signaling is a necessary mechanism to trigger or even amplify cell communication. Its ligands, notably adenosine triphosphate (ATP) and adenosine, modulate... (Review)
Review
Purinergic signaling is a necessary mechanism to trigger or even amplify cell communication. Its ligands, notably adenosine triphosphate (ATP) and adenosine, modulate specific membrane-bound receptors in virtually all human cells. Regardless of the stage of the pregnancy, cellular communication between maternal, placental, and fetal cells is the paramount mechanism to sustain its optimal status. In this review, we describe the crucial role of purinergic signaling on the regulation of the maternal-fetal trophic exchanges, immune control, and endocrine exchanges throughout pregnancy. The nature of the modulation of both ATP and adenosine on the embryo-maternal interface, going through placental invasion until birth delivery depends on the general maternal-fetal health state and consequently on the selective activation of their specific receptors. In addition, an increasing number of studies have been demonstrating the pivotal role of ATP and adenosine in modulating deleterious effects of suboptimal conditions of pregnancy. Here, we discuss the role of purinergic signaling on the balance that coordinates the embryo-maternal exchanges and a promising therapeutic venue in the context of pregnancy disorders.
Topics: Adenosine; Adenosine Triphosphate; Female; Fetus; Humans; Placenta; Pregnancy; Signal Transduction
PubMed: 34596240
DOI: 10.1002/jcp.30594 -
Purinergic Signalling Mar 2023Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension... (Review)
Review
Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. AR, AR, AR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.
Topics: Humans; Endothelial Cells; Receptors, Purinergic; Synaptic Transmission; Signal Transduction; Hypertension; Adenosine Triphosphate
PubMed: 35181831
DOI: 10.1007/s11302-022-09852-8