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Reproduction, Fertility, and Development Jun 2024In addition to its central role in cellular metabolism, adenosine 5'-triphosphate (ATP) is an important extracellular signalling molecule involved in various... (Review)
Review
In addition to its central role in cellular metabolism, adenosine 5'-triphosphate (ATP) is an important extracellular signalling molecule involved in various physiological processes. In reproduction, extracellular ATP participates in both autocrine and paracrine paths regulating gametogenesis, gamete maturation and fertilisation. This review focusses on how extracellular ATP modulates sperm physiology with emphasis on the mammalian acrosome reaction. The presence of extracellular ATP in the reproductive tract is primarily determined by the ion channels and transporters that influence its movement within the cells comprising the tract. The main targets of extracellular ATP in spermatozoa are its own transporters, particularly species-specific sperm purinergic receptors. We also discuss notable phenotypes from knock-out mouse models and human Mendelian inheritance related to ATP release mechanisms, along with immunological, proteomic, and functional observations regarding sperm purinergic receptors and their involvement in sperm signalling.
Topics: Animals; Male; Spermatozoa; Adenosine Triphosphate; Humans; Acrosome Reaction; Receptors, Purinergic; Signal Transduction; Mammals; Mice
PubMed: 38870344
DOI: 10.1071/RD23227 -
International Journal of Molecular... May 2024Metals are dispersed in natural environments, particularly in the aquatic environment, and accumulate, causing adverse effects on aquatic life. Moreover, chronic... (Review)
Review
Metals are dispersed in natural environments, particularly in the aquatic environment, and accumulate, causing adverse effects on aquatic life. Moreover, chronic polymetallic water pollution is a common problem, and the biological effects of exposure to complex mixtures of metals are the most difficult to interpret. In this review, metal toxicity is examined with a focus on its impact on energy metabolism. Mechanisms regulating adenosine triphosphate (ATP) production and reactive oxygen species (ROS) emission are considered in their dual roles in the development of cytotoxicity and cytoprotection, and mitochondria may become target organelles of metal toxicity when the transmembrane potential is reduced below its phosphorylation level. One of the main consequences of metal toxicity is additional energy costs, and the metabolic load can lead to the disruption of oxidative metabolism and enhanced anaerobiosis.
Topics: Animals; Adenosine Triphosphate; Energy Metabolism; Fishes; Metals; Mitochondria; Oxidative Stress; Reactive Oxygen Species; Water Pollutants, Chemical
PubMed: 38732234
DOI: 10.3390/ijms25095015 -
Biosensors & Bioelectronics Nov 2023MicroRNAs (miRNAs) have emerged as important biomarkers in biomedicine and bioimaging due to their roles in various physiological and pathological processes. Real-time... (Review)
Review
MicroRNAs (miRNAs) have emerged as important biomarkers in biomedicine and bioimaging due to their roles in various physiological and pathological processes. Real-time and in situ monitoring of dynamic fluctuation of miRNAs in living cells is crucial for understanding these processes. However, current miRNA imaging probes still have some limitations, including the lack of effective amplification methods for low abundance miRNAs bioanalysis and uncontrollable activation, leading to background signals and potential false-positive results. Therefore, researchers have been integrating activatable devices with miRNA amplification techniques to design stimuli-responsive nanoprobes for "on-demand" and precise imaging of miRNAs in living cells. In this review, we summarize recent advances of stimuli-responsive probes for the amplification-based imaging of miRNAs in living cells and discuss the future challenges and opportunities in this field, aiming to provide valuable insights for accurate disease diagnosis and monitoring.
Topics: Humans; MicroRNAs; Gene Amplification; Cell Survival; Adenosine Triphosphate; Hydrogen-Ion Concentration
PubMed: 37619479
DOI: 10.1016/j.bios.2023.115584 -
The Journal of Neuroscience : the... Aug 2023Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache...
Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache phase in migraine by promoting the activation and mechanical sensitization of trigeminal primary afferent nociceptive neurons that innervate the cranial meninges. The factors underlying meningeal nociception in the wake of CSD remain poorly understood but potentially involve the parenchymal release of algesic mediators and damage-associated molecular patterns, particularly ATP. Here, we explored the role of ATP-P2X purinergic receptor signaling in mediating CSD-evoked meningeal afferent activation and mechanical sensitization. Male rats were subjected to a single CSD episode. , extracellular single-unit recording was used to measure meningeal afferent ongoing activity changes. Quantitative mechanical stimuli using a servomotor force-controlled stimulator assessed changes in the afferent's mechanosensitivity. Manipulation of meningeal P2X receptors was achieved via local administration of pharmacological agents. Broad-spectrum P2X receptor inhibition, selective blockade of the P2X7 receptor, and its related Pannexin 1 channel suppressed CSD-evoked afferent mechanical sensitization but did not affect the accompanying afferent activation response. Surprisingly, inhibition of the pronociceptive P2X2/3 receptor did not affect the activation or sensitization of meningeal afferents post-CSD. P2X7 signaling underlying afferent mechanosensitization was localized to the meninges and did not affect CSD susceptibility. We propose that meningeal P2X7 and Pannexin 1 signaling, potentially in meningeal macrophages or neutrophils, mediates the mechanical sensitization of meningeal afferents, which contributes to migraine pain by exacerbating the headache during normally innocuous physical activities. Activation and sensitization of meningeal afferents play a key role in migraine headache, but the underlying mechanisms remain unclear. Here, using a rat model of migraine with aura involving cortical spreading depolarization (CSD), we demonstrate that meningeal purinergic P2X7 signaling and its related Pannexin 1 pore, but not nociceptive P2X2/3 receptors, mediate prolonged meningeal afferent sensitization. Additionally, we show that meningeal P2X signaling does not contribute to the increased afferent ongoing activity in the wake of CSD. Our finding points to meningeal P2X7 signaling as a critical mechanism underlying meningeal nociception in migraine, the presence of distinct mechanisms underlying the activation and sensitization of meningeal afferents in migraine, and highlight the need to target both processes for effective migraine therapy.
Topics: Rats; Male; Animals; Nociceptors; Migraine Disorders; Meninges; Headache; Adenosine Triphosphate
PubMed: 37487740
DOI: 10.1523/JNEUROSCI.0368-23.2023 -
Organic & Biomolecular Chemistry Aug 2023We serendipitously found that chaperonin GroEL can hydrolyze -nitrophenyl β-galactoside (ONPG), a well-known substrate of the enzyme β-galactosidase. The ONPG...
We serendipitously found that chaperonin GroEL can hydrolyze -nitrophenyl β-galactoside (ONPG), a well-known substrate of the enzyme β-galactosidase. The ONPG hydrolysis by GroEL follows typical enzyme kinetics. Our experiments and molecular docking studies suggest ONPG binding at the ATP binding site of GroEL.
Topics: Molecular Docking Simulation; Binding Sites; Galactosides; Chaperonins; Adenosine Triphosphate; Protein Folding; Hydrolysis
PubMed: 37464895
DOI: 10.1039/d3ob00989k -
European Journal of Medicinal Chemistry Oct 2023Tumors, a disease with a high mortality rate worldwide, have become a serious threat to human health. Exonucleotide-5'-nucleotidase (CD73) is an emerging target for... (Review)
Review
Tumors, a disease with a high mortality rate worldwide, have become a serious threat to human health. Exonucleotide-5'-nucleotidase (CD73) is an emerging target for tumor therapy. Its inhibition can significantly reduce adenosine levels in the tumor microenvironment. It has a better therapeutic effect on adenosine-induced immunosuppression. In the immune response, extracellular ATP exerts immune efficacy by activating T cells. However, dead tumor cells release excess ATP, overexpress CD39 and CD73 on the cell membrane and catabolize this ATP to adenosine. This leads to further immunosuppression. There are a number of inhibitors of CD73 currently under investigation. These include antibodies, synthetic small molecule inhibitors and a number of natural compounds with prominent roles in the anti-tumor field. However, only a small proportion of the CD73 inhibitors studied to date have successfully reached the clinical stage. Therefore, effective and safe inhibition of CD73 in oncology therapy still holds great therapeutic potential. This review summarizes the currently reported CD73 inhibitors, describes their inhibitory effects and pharmacological mechanisms, and provides a brief review of them. It aims to provide more information for further research and development of CD73 inhibitors.
Topics: Humans; 5'-Nucleotidase; Adenosine; Immunotherapy; Neoplasms; Antibodies; Adenosine Triphosphate; Tumor Microenvironment
PubMed: 37302340
DOI: 10.1016/j.ejmech.2023.115546 -
Biotechnology Advances 2024Adenosine triphosphate (ATP) regeneration is a significant step in both living cells and in vitro biotransformation (ivBT). Rotary motor ATP synthases (ATPases), which... (Review)
Review
Adenosine triphosphate (ATP) regeneration is a significant step in both living cells and in vitro biotransformation (ivBT). Rotary motor ATP synthases (ATPases), which regenerate ATP in living cells, have been widely assembled in biomimetic structures for in vitro ATP synthesis. In this review, we present a comprehensive overview of ATPases, including the working principle, orientation and distribution density properties of ATPases, as well as the assembly strategies and applications of ATPase-based ATP regeneration modules. The original sources of ATPases for in vitro ATP regeneration include chromatophores, chloroplasts, mitochondria, and inverted Escherichia coli (E. coli) vesicles, which are readily accessible but unstable. Although significant advances have been made in the assembly methods for ATPase-artificial membranes in recent decades, it remains challenging to replicate the high density and orientation of ATPases observed in vivo using in vitro assembly methods. The use of bioproton pumps or chemicals for constructing proton motive forces (PMF) enables the versatility and potential of ATPase-based ATP regeneration modules. Additionally, overall robustness can be achieved via membrane component selection, such as polymers offering great mechanical stability, or by constructing a solid supporting matrix through layer-by-layer assembly techniques. Finally, the prospects of ATPase-based ATP regeneration modules can be expected with the technological development of ATPases and artificial membranes.
Topics: Biotransformation; Adenosine Triphosphate; Adenosine Triphosphatases; Escherichia coli
PubMed: 38763231
DOI: 10.1016/j.biotechadv.2024.108377 -
CNS Neuroscience & Therapeutics Feb 2024Depression is a prevalent psychiatric disorder with high long-term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the... (Review)
Review
BACKGROUND
Depression is a prevalent psychiatric disorder with high long-term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti-depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about "ATP and depression" especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression.
AIM
Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression.
CONCLUSION
We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression.
Topics: Humans; Adenosine Triphosphate; Depression; Astrocytes
PubMed: 38375982
DOI: 10.1111/cns.14536 -
Nature Communications Jul 2023Energy-coupling factor (ECF)-type transporters mediate the uptake of micronutrients in many bacteria. They consist of a substrate-translocating subunit (S-component) and...
Energy-coupling factor (ECF)-type transporters mediate the uptake of micronutrients in many bacteria. They consist of a substrate-translocating subunit (S-component) and an ATP-hydrolysing motor (ECF module) Previous data indicate that the S-component topples within the membrane to alternately expose the binding site to either side of the membrane. In many ECF transporters, the substrate-free S-component can be expelled from the ECF module. Here we study this enigmatic expulsion step by cryogenic electron microscopy and reveal that ATP induces a concave-to-convex shape change of two long helices in the motor, thereby destroying the S-component's docking site and allowing for its dissociation. We show that adaptation of the membrane morphology to the conformational state of the motor may favour expulsion of the substrate-free S-component when ATP is bound and docking of the substrate-loaded S-component after hydrolysis. Our work provides a picture of bilayer-assisted chemo-mechanical coupling in the transport cycle of ECF transporters.
Topics: Bacterial Proteins; Protein Conformation; Bacteria; Biological Transport; Adenosine Triphosphate
PubMed: 37491368
DOI: 10.1038/s41467-023-40266-1 -
Current Opinion in Biotechnology Dec 2023Nucleotide metabolism plays a crucial role in the regulation of the tumor microenvironment (TME) and immune cell function. In the TME, limited availability of nucleotide... (Review)
Review
Nucleotide metabolism plays a crucial role in the regulation of the tumor microenvironment (TME) and immune cell function. In the TME, limited availability of nucleotide precursors due to increased consumption by tumor cells and T cells affects both tumor development and immune function. Metabolic reprogramming in tumor cells favors pathways supporting growth and proliferation, including nucleotide synthesis. Additionally, extracellular nucleotides, such as ATP and adenosine, exhibit dual roles in modulating immune function and tumor cell survival. ATP stimulates antitumor immunity by activating purinergic receptors, while adenosine acts as a potent immunosuppressor. Targeting nucleotide metabolism in the TME holds immense promise for cancer therapy. Understanding the intricate relationship between nucleotide metabolism, the TME, and immune responses will pave the way for innovative therapeutic interventions.
Topics: Humans; Tumor Microenvironment; Neoplasms; Adenosine; Adenosine Triphosphate; Nucleotides
PubMed: 37863018
DOI: 10.1016/j.copbio.2023.103008