Mesut Parlak, Ziad Joha, Fatih Yulak, Ali Sefa Mendil, Yaşar Taştemur
{"title":"Lycopene induces antiproliferative effects through apoptosis, autophagy, and oxidative DNA damage in the HeLa cells.","authors":"Mesut Parlak, Ziad Joha, Fatih Yulak, Ali Sefa Mendil, Yaşar Taştemur","doi":"10.1080/10799893.2024.2426516","DOIUrl":"10.1080/10799893.2024.2426516","url":null,"abstract":"<p><strong>Background: </strong>This study explores the role of apoptosis, autophagy, and oxidative DNA damage in influencing the cytotoxic impact of lycopene on HeLa cells.</p><p><strong>Material and methods: </strong>Cell viability following exposure to varying lycopene concentrations was determined using an XTT assay. ELISA measured key cell death proteins (Bax, BCL-2, etc.), while immunofluorescence staining visualized LC3β (autophagy) and 8-oxo-dG (DNA damage).</p><p><strong>Results: </strong>Lycopene significantly killed HeLa cells in a dose-dependent way (IC50 = 10 μM). Subsequent examinations conducted with the IC50 dose of lycopene demonstrated a notable elevation in the expression levels of apoptotic proteins, such as cleaved caspase 3, cleaved PARP, and Bax (<i>p</i> < 0.001). Additionally, treatment with this substance led to an increase in the levels of 8-oxo-dG (<i>p</i> < 0.001), a widely acknowledged biomarker indicative of oxidative DNA damage. Furthermore, a significant rise (<i>p</i> < 0.05) in LC3β protein levels, a well-established indicator of autophagy activation, was noted.</p><p><strong>Conclusion: </strong>This study suggests lycopene's potential to fight cervical cancer by triggering programmed cell death (apoptosis) and cellular self-digestion (autophagy). These findings highlight lycopene as a promising candidate for future cervical cancer treatments.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"115-121"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoli Zou, Maoyan Wu, Mengqin Tu, Xiaozhen Tan, Yang Long, Yong Xu, Mingxiu Li
{"title":"4-octyl itaconate inhibits high glucose induced renal tubular epithelial cell fibrosis through TGF-β-ROS pathway","authors":"Xiaoli Zou, Maoyan Wu, Mengqin Tu, Xiaozhen Tan, Yang Long, Yong Xu, Mingxiu Li","doi":"10.1080/10799893.2024.2341678","DOIUrl":"https://doi.org/10.1080/10799893.2024.2341678","url":null,"abstract":"Diabetic kidney disease (DKD) is one of the most serious complications of diabetes and has become the leading cause of end-stage kidney disease, causing serious health damage and a huge economic bu...","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"31 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140803085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zafer Sahin, Osman Aktas, Omer Faruk Kalkan, Gokhan Cuce, Ahmet Alver, Elif Sahin, Seniz Erdem, Neslihan Saglam, Zulfikare Isik Solak Gormus, Selim Kutlu
{"title":"Intracerebroventricular injection of kisspeptin in male rats activates hypothalamo-pituitary-gonadal axis, but not hypothalamo-pituitary-adrenal axis","authors":"Zafer Sahin, Osman Aktas, Omer Faruk Kalkan, Gokhan Cuce, Ahmet Alver, Elif Sahin, Seniz Erdem, Neslihan Saglam, Zulfikare Isik Solak Gormus, Selim Kutlu","doi":"10.1080/10799893.2024.2333470","DOIUrl":"https://doi.org/10.1080/10799893.2024.2333470","url":null,"abstract":"Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise...","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"1 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Low pH modulates lipopolysaccharide-induced tumor necrosis factor-alpha expression and macropinocytotic activity in RAW264.7 cells.","authors":"Miku Otsugu, Ayumi Mine, Izumi Uchida, Yuta Miyake, Ryo Tachihara, Kurumi Fujiwara, Ayako Ichimura, Koichi Sato, Hideaki Tomura","doi":"10.1080/10799893.2024.2395310","DOIUrl":"10.1080/10799893.2024.2395310","url":null,"abstract":"<p><p>Inflammation triggers various types of diseases that need to be addressed. Macrophages play important roles in the inflammatory responses. As atherosclerosis progresses, macrophages transform into foam cells. Extracellular acidification is observed at and around bacterial infection and atherosclerotic sites. However, the effects of acidification on the inflammatory response of macrophages and the progression of atherosclerosis have not been fully understood. This study investigates the impact of extracellular acidification on lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) expression and macropinocytotic activity in RAW264.7 cells. TNF-α expression is measured by real-time polymerase chain reaction (relative value to glyceraldehyde-3-phosphate dehydrogenase expression). Macropinocytotic activity is measured by neutral red uptake (absorbance at 540 nm). Results show that TNF-α expression increased with decreasing extracellular pH in both un-foamed and foamed cells. Macropinocytotic activity was upregulated at pH 6.8 in un-foamed cells, but downregulated in foamed cells stimulated at low pH. Proton-sensing G protein-coupled receptors (GPCRs) were involved in the expression of TNF-α and in the macropinocytotic activity of foamed cells. In conclusion, this study reveals that extracellular acidification differently affect various inflammatory responses such as LPS-induced TNF-α expression and macropinocytotic activity of RAW264.7 cells and different proton-sensing GPCRs are involved in the different inflammatory responses.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"63-71"},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Musab Ali, Zhichao Zhang, Mahmoud A A Ibrahim, Mahmoud E S Soliman
{"title":"Heat shock protein (Hsp27)-ceramide synthase (Cers1) protein-protein interactions provide a new avenue for unexplored anti-cancer mechanism and therapy.","authors":"Musab Ali, Zhichao Zhang, Mahmoud A A Ibrahim, Mahmoud E S Soliman","doi":"10.1080/10799893.2024.2392711","DOIUrl":"10.1080/10799893.2024.2392711","url":null,"abstract":"<p><p>Hsp27 is a member of the small heat-shock proteins (sHSPs) - the known cellular line of defence against abnormal protein folding behaviors. Nevertheless, its upregulation is linked to a variety of pathological disorders, including several types of cancers. The ceramide synthases (CerS) mediate the synthesis of ceramide, a critical structural and signaling lipid. Functionally, downstream ceramide metabolites are implicated in the apoptosis process and their abnormal functionality has been linked to anticancer resistance. Studies showed that CerS1 are possibly inhibited by Hsp27 leading to biochemical anticancer effects <i>in vitro</i>. Nevertheless, the nature of such protein-protein interaction (PPI) has not been considerably investigated in molecular terms, hence, we present the first description of the dynamics CerS1-Hsp27 interaction landscapes using molecular dynamics simulations. Time-scale molecular dynamics simulation analysis indicated a system-wide conformational events of decreased stability, increased flexibility, reduced compactness, and decreased folding of CerS1. Analysis of binding energy showed a favorable interaction entailing 56 residues at the interface and a total stabilizing energy of -158 KJ/mol. The CerS1 catalytic domain experienced an opposite trend compared to the protein backbone. Yet, these residues adopted a highly compact conformation as per DCCM and DSSP analysis. Furthermore, conserved residues (SER 212, ASP 213, ALA 240, GLY 243, ASP 319) comprising the substrate shuttling machinery showed notable rigidity implying a restrained ceramide precursor access and assembly; hence, a possible inhibitory mechanism. Findings from this report would streamline a better molecular understanding of CerS1-Hsp27 interactions and decipher its potential avenue toward unexplored anti-cancer mechanisms and therapy.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"41-53"},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The vasodilator effect of Eugenol on uterine artery - potential therapeutic applications in pregnancy-associated hypertension.","authors":"Harithalakshmi Jandhyam, Bimal Prasanna Mohanty, Subas Chandra Parija","doi":"10.1080/10799893.2024.2395301","DOIUrl":"10.1080/10799893.2024.2395301","url":null,"abstract":"<p><p>Preeclampsia, a gestational associated hypertension, has been reported in 6-8% of pregnant women worldwide leading to premature delivery and low birth weight of newborn due to reduced blood flow to placenta. Although several vasodilators (Methyl dopa, hydralazine, β-blockers and diuretics) are currently in use to treat preeclampsia, still there is a search for safer drugs with better efficacy. Lately, antihypertensive vasodilators from natural sources are gaining importance in treating preeclampsia. Eugenol (Eug), a natural essential oil, has been traditionally used in health and food products without any risk. In the present study, <i>ex vivo</i> experiments were designed to examine the vasorelaxation effect of Eug and its signaling pathways in a middle uterine artery (MUA) of pregnant <i>Capra hircus</i> (<i>Ch</i>). In presence of different blockers (L-NAME, indomethacin, ODQ, Ouabain, glibenclamide, 4-AP, Ba<sup>2</sup>, Carbenoxolone and 18β Glycyrrhetinic acid), Eug-induced concentration-dependent vasorelaxation response was elicited. The results showed that Eug caused a greater vasorelaxation effect in the MU of pregnant animals, which is mediated by potential activation of eNOS, K<sub>ATP</sub> channels, and K<sub>ir</sub> channels with moderate activation of Na<sup>+</sup>- K<sup>+</sup>- ATPase and sGC and MEGJ. These findings provide a strong basis for developing Eug as a therapeutic candidate in the treatment of pregnancy-associated hypertension.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"54-62"},"PeriodicalIF":2.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nazar M Shareef Mahmood, Almas Mr Mahmud, Ismail M Maulood
{"title":"The roles of angiotensin-converting enzyme 2 inhibitor, melatonin and its agonist on angiotensin II reactivity in intact and denuded rat aortic rings.","authors":"Nazar M Shareef Mahmood, Almas Mr Mahmud, Ismail M Maulood","doi":"10.1080/10799893.2024.2345907","DOIUrl":"10.1080/10799893.2024.2345907","url":null,"abstract":"<p><strong>Background: </strong>The pineal product melatonin (MEL) modulates blood vessels through G protein-coupled receptors (GPCRs) called melatonin type 1 receptor (MT<sub>1</sub>R) and melatonin type 2 receptor (MT<sub>2</sub>R), in that order. The renin-angiotensin system (RAS), which breaks down angiotensin II (Ang II) to create Ang 1-7, is thought to be mostly controlled by angiotensin-converting enzyme-2 (ACE<sub>2</sub>).</p><p><strong>Aim: </strong>The current work examines the involvement of ACE<sub>2</sub> inhibitor, MEL, and ramelteon (RAM) in the vascular response to Ang II activities in the endothelial denuded (E-) and intact (E+) rat isolated thoracic aortic rings.</p><p><strong>Method: </strong>The isometric tension was measured to evaluate the vascular Ang II contractility using dose response curve (DRC).</p><p><strong>Results: </strong>MEL and RAM caused a rightward shift of Ang II in endothelium E + and endothelium E- aorta.</p><p><strong>Conclusion: </strong>According to the current study, the distribution of MEL receptors and the endothelium's condition are related to the vasomodulatory effect of MEL and ACE<sub>2</sub> on Ang II attenuation. These physiological interactions can control vascular tone and increase Ang II reactivity denude endothelial layaer.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"35-40"},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arushi Chauhan, Jitender Singh, Namrata Sangwan, Pramod K Avti
{"title":"Mechanistic insights into sodium ion-mediated ligand binding affinity and modulation of 5-HT2B GPCR activity: implications for drug discovery and development.","authors":"Arushi Chauhan, Jitender Singh, Namrata Sangwan, Pramod K Avti","doi":"10.1080/10799893.2024.2332886","DOIUrl":"10.1080/10799893.2024.2332886","url":null,"abstract":"<p><strong>Purpose: </strong>The G-protein coupled receptor (GPCR) family, implicated in neurological disorders and drug targets, includes the sensitive serotonin receptor subtype, 5-HT2B. The influence of sodium ions on ligand binding at the receptor's allosteric region is being increasingly studied for its impact on receptor structure.</p><p><strong>Methods: </strong>High-throughput virtual screening of three libraries, specifically the Asinex-GPCR library, which contains 8,532 compounds and FDA-approved (2466 compounds) and investigational compounds (2731)) against the modeled receptor [4IB4-5HT<sub>2B</sub>R<sub>M</sub>] using the standard agonist/antagonist (Ergotamine/Methysergide), as previously selected from our studies based on ADMET profiling, and further on basis of binding free energy a single compound - dihydroergotamine is chosen.</p><p><strong>Results: </strong>This compound displayed strong interactions with the conserved active site. Ions influence ligand binding, with stronger interactions (3-H-bonds and 1-π-bond around 3.35 Å) observed when an agonist and ions are present. Ions entry is guided by conserved motifs in helices III, IV, and VII, which regulate the receptor. Dihydroergotamine, the selected drug, showed binding variance based on ions presence/absence, affecting amino acid residues in these motifs. DCCM and PCA confirmed the stabilization of ligands, with a greater correlation (∼46.6%-PC1) observed with ions. Dihydroergotamine-modified interaction sites within the receptor necessary for activation, serving as a potential 5HT<sub>2B</sub>R<sub>M</sub> agonist. RDF analysis showed the sodium ions density around the active site during dihydroergotamine binding.</p><p><strong>Conclusion: </strong>Our study provides insights into sodium ion mobility's role in controlling ligand binding affinity in 5HT<sub>2B</sub>R, offering therapeutic development insights.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"8-18"},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"cGAS-STING and PD1/PDL-1 pathway in breast cancer: a window to new therapies.","authors":"Milad Khorasani, Maryam Alaei","doi":"10.1080/10799893.2024.2325353","DOIUrl":"10.1080/10799893.2024.2325353","url":null,"abstract":"<p><p>Breast cancer is a complex malignancy with diverse molecular and cellular subtypes and clinical outcomes. Despite advances in treatment, breast cancer remains a significant health challenge. However, recent advances in cancer immunotherapy have shown promising results in the treatment of breast cancer, particularly the use of inhibitors that target the immune checkpoint PD1/PDL1. Also, the cGAS-STING pathway, an important part of the innate immune response, has been considered as a major potential therapeutic target for breast cancer. In this narrative review, we provide an overview of the cGAS-STING and PD1/PDL-1 pathway in breast cancer, including their role in tumor development, progression, and response to treatment. We also discuss potential future directions for research.</p>","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":" ","pages":"1-7"},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The route of autophagy regulation by osteopontin: a review on the linking mechanisms","authors":"Zohreh Abdolvahabi, Samira Ezzati-Mobaser, Zahra Hesari","doi":"10.1080/10799893.2023.2291563","DOIUrl":"https://doi.org/10.1080/10799893.2023.2291563","url":null,"abstract":"Autophagy is a dynamic intracellular process of protein degradation, which is mostly triggered by nutrient deprivation. This process initiates with the formation of autophagosomes, which they captu...","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"18 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}