Production, characterization, and application of a monoclonal antibody specific for the extracellular domain of human P2X7R

Li, Mingxuan; Luo, Shuping; Zhang, Yunfang; Jia, Lina; Yang, Chuanyu; Peng, Xiaoxiang; Zhao, Ronglan

doi:10.1007/s00253-019-10340-0

Cited by 7 publications

(6 citation statements)

References 53 publications

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“…Available antibodies against the P2X7 receptor are polyclonal, which are prone to cross-reactivity, or monoclonal. Although they did not detect P2X7 receptors in knockout (KO) mice, these monoclonal antibodies failed to consistently and reliably detect and/or block P2X7 receptor signaling pathway in WT mice (Sim et al, 2004;Li et al, 2020). There are at least two P2X7 receptor KO mice commercially available.…”

Section: The P2x7 Receptormentioning

confidence: 99%

The P2X7 Receptor: Central Hub of Brain Diseases

Andrejew

Oliveira-Giacomelli

Ribeiro

et al. 2020

Front. Mol. Neurosci.

112

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The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the extracellular milieu. The P2X7 receptor is widely expressed in the CNS, such as frontal cortex, hippocampus, amygdala and striatum, regions involved in neurodegenerative diseases and psychiatric disorders. Despite P2X7 receptor functions in glial cells have been extensively studied, the existence and roles of this receptor in neurons are still controversially discussed. Regardless, P2X7 receptors mediate several processes observed in neuropsychiatric disorders and brain tumors, such as activation of neuroinflammatory response, stimulation of glutamate release and neuroplasticity impairment. Moreover, P2X7 receptor gene polymorphisms have been associated to depression, and isoforms of P2X7 receptors are implicated in neuropsychiatric diseases. In view of that, the P2X7 receptor has been proposed to be a potential target for therapeutic intervention in brain diseases. This review discusses the molecular mechanisms underlying P2X7 receptor-mediated signaling in neurodegenerative diseases, psychiatric disorders, and brain tumors. In addition, it highlights the recent advances in the development of P2X7 receptor antagonists that are able of penetrating the central nervous system.

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Section: The P2x7 Receptormentioning

confidence: 99%

The P2X7 Receptor: Central Hub of Brain Diseases

Andrejew

Oliveira-Giacomelli

Ribeiro

et al. 2020

Front. Mol. Neurosci.

112

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“…Evidence indicates that P2X7R expression appears to be epigenetically regulated by DNA methylation [ 19 ] and miRNA regulation [ 20 ], which are important processes for gene expression regulation in a variety of cell types [ 21 , 22 , 23 , 24 , 25 ]. The P2X7R full-length isoform consists of a sequence of 595 amino acid (a.a.) residues, in which two hydrophobic regions crossing the plasma membrane can be identified: (i) N-terminus (N-ter), which is located in the cytoplasm; (ii) C-terminus (C-ter), which contains 70 to 200 additional a.a. residues compared to other P2X family receptors [ 26 , 27 ]. The extracellular domain contains the ATP binding site and 10 cysteine residues whose oxidation contributes to the sulphide bridge formation, which is necessary for the tertiary structure [ 26 ].…”

Section: P2x7 Receptor Genetics Characteristics Function and Tissue D...mentioning

confidence: 99%

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

Rotondo

Mazziotta

Lanzillotti

et al. 2022

Cancers

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The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to a variety of cellular processes, while its dysregulation has been linked to inflammation and cancer. P2X7R is expressed in cancer and immune system cell surfaces. ATP plays a key role in numerous metabolic processes due to its abundance in the tumour microenvironment. P2X7R plays an important role in cancer by interacting with ATP. The unusual property of P2X7R is that stimulation with low doses of ATP causes the opening of a permeable channel for sodium, potassium, and calcium ions, whereas sustained stimulation with high doses of ATP favours the formation of a non-selective pore. The latter effect induces a change in intracellular homeostasis that leads to cell death. This evidence suggests that P2X7R has both pro- and anti-tumour proprieties. P2X7R is increasingly recognised as a regulator of inflammation. In this review, we aimed to describe the most relevant characteristics of P2X7R function, activation, and its ligands, while also summarising the role of P2X7R activation in the context of inflammation and cancer. The currently used therapeutic approaches and clinical trials of P2X7R modulators are also described.

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“…The oncological conditions, in which P2X7 receptor antagonism were efficacious in reducing cancer progression include, but are not limited to, breast cancer [ 88 , 89 ], melanoma [ 90 , 91 , 92 ], neuroblastoma [ 20 ], mesothelioma [ 8 ], glioma [ 93 ] and AML [ 79 , 80 , 81 , 92 ]. Notably, the P2X7 receptor antagonism reduced cancer aggressiveness acting at metabolic pathways in some of these models, such as AML, neuroblastoma and glioma [ 20 , 81 , 83 , 94 ].…”

Section: Anti-p2x7 Receptor Drugs In Effectivity Studies or In Use For Cancer Therapymentioning

confidence: 99%

“…Moreover, a high-affinity monoclonal antibody (4B3A4 mAb) was designed for blocking the human P2X7 receptor, by binding to its extracellular domain. P2X7 receptor activity was effectively blocked by the 4B3A4 mAb, once Ca 2+ entry and YO-PRO-1 uptake stimulated by ATP were significantly reduced [ 94 ], making this compound promising for cancer therapy.…”

Section: Anti-p2x7 Receptor Drugs In Effectivity Studies or In Use For Cancer Therapymentioning

confidence: 99%

Cancer Metabostemness and Metabolic Reprogramming via P2X7 Receptor

Rabelo

Arnaud-Sampaio

Adinolfi

et al. 2021

Cells

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The heterogeneity of tumor cell mass and the plasticity of cancer cell phenotypes in solid tumors allow for the insurgence of resistant and metastatic cells, responsible for cancer patients’ clinical management’s main challenges. Among several factors that are responsible for increased cancer aggression, metabolic reprogramming is recently emerging as an ultimate cancer hallmark, as it is central for cancer cell survival and self-renewal, metastasis and chemoresistance. The P2X7 receptor, whose expression is upregulated in many solid and hematological malignancies, is also emerging as a good candidate in cancer metabolic reprogramming and the regulation of stem cell proliferation and differentiation. Metabostemness refers to the metabolic reprogramming of cancer cells toward less differentiated (CSCs) cellular states, and we believe that there is a strong correlation between metabostemness and P2X7 receptor functions in oncogenic processes. Here, we summarize important aspects of P2X7 receptor functions in normal and tumor tissues as well as essential aspects of its structure, regulation, pharmacology and its clinical use. Finally, we review current knowledge implicating P2X7 receptor functions in cancer-related molecular pathways, in metabolic reprogramming and in metabostemness.

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Production, characterization, and application of a monoclonal antibody specific for the extracellular domain of human P2X7R

Cited by 7 publications

References 53 publications

The P2X7 Receptor: Central Hub of Brain Diseases

The P2X7 Receptor: Central Hub of Brain Diseases

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

Cancer Metabostemness and Metabolic Reprogramming via P2X7 Receptor

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