Expression, Distribution and Function of the Transient Receptor Potential Vanilloid Type 1 (TRPV1) in Endometrial Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3104 - 3104

Published: March 27, 2025

The transient receptor potential vanilloid 1 (TRPV1) is a calcium-sensitive membrane activated by capsaicin and the endocannabinoid, anandamide (AEA). Once in vitro, endometrial cancer (EC) cell growth appears to be inhibited through increased apoptosis, but mechanism remains unclear. Our aim was investigate expression distribution of TRPV1 normal cancerous endometria determine precise vitro decreased EC cellular growth. patients with carcinoma (15 Type EC, six 2 EC) (atrophic endometria) assessed using quantitative RT-PCR immunohistochemistry (IHC). Additionally, immunohistochemical staining for proliferation marker Ki-67, pro-apoptotic BAX anti-apoptotic Bcl-2 were explored. transcript (p = 0.0054) immunoreactive protein < 0.0001) levels significantly reduced all tissues when compared control (atrophic) endometria. almost 50% reduction mirrored an complete loss protein. (Ki-67) correlated mutated inversely Bcl-2, only samples. In AEA caused decrease Ishikawa numbers, whilst did not, suggesting anti-proliferative effect cells not via receptor. conclusion, vivo plays role aetiopathogenesis EC. Activation also probably promotes involving TRPV1.

Language: Английский

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From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling

Molecules, Journal Year: 2024, Volume and Issue: 29(15), P. 3694 - 3694

Published: Aug. 4, 2024

2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It synthesized on demand in postsynaptic membranes through sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations PLC DAGL isoforms, well additional intracellular pathways implying other enzymes substrates. Three alternative synthesis rest extracellular cleavage 2-arachidonoyl-lysophospholipids by three different hydrolases: glycerophosphodiesterase 3 (GDE3), lipid phosphate phosphatases (LPPs), two members ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP6-7). We propose names AlterAG-1, -2, -3 for sharing an ectocellular localization, allowing them convert lysophospholipid mediators into 2-AG, thus inducing typical switches between G-protein-coupled receptors (GPCRs). This implies critical importance regioisomerism (LPLs) which object deep analysis within this review. The precise functional roles AlterAGs are still poorly understood will require gene invalidation approaches, knowing that its related lysophospholipids involved numerous aspects physiology pathology, including cancer, inflammation, immune defenses, obesity, bone development, neurodegeneration, or psychiatric disorders.

Language: Английский

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Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(10), P. 11646 - 11664

Published: Oct. 19, 2024

Neurodegenerative disorders, particularly Alzheimer's and Parkinson's diseases, continue to challenge modern medicine despite therapeutic advances. Orphan G-protein-coupled receptors (GPCRs) have emerged as promising targets in the central nervous system, offering new avenues for drug development. This review focuses on structural biology of orphan GPCRs implicated these providing a comprehensive analysis their molecular architecture functional mechanisms. We examine recent breakthroughs determination techniques, such cryo-electron microscopy X-ray crystallography, which elucidated intricate conformations receptors. The highlights how insights inform our understanding GPCR activation, ligand binding signaling pathways. By integrating data with pharmacology, we explore potential structure-guided approaches developing targeted therapeutics toward GPCRs. structural-biology-centered perspective aims deepen comprehension guide future discovery efforts neurodegenerative disorders.

Language: Английский

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Structure basis of ligand recognition and activation of GPR55

Cell Research, Journal Year: 2024, Volume and Issue: 35(1), P. 80 - 83

Published: Oct. 31, 2024

Language: Английский

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