{"title":"Molecular mechanisms of diabetic nephropathy: A narrative review","authors":"Tian Sun, Yina Guo, Yanting Su, Shigang Shan, Wenbin Qian, Feixue Zhang, Mengxi Li, Zhenwang Zhang","doi":"10.1002/cbin.12212","DOIUrl":"10.1002/cbin.12212","url":null,"abstract":"<p>Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end-stage renal disease. It is attracting significant attention in both domestic and international research due to its widespread occurrence, fast advancement, and limited choices for prevention and treatment. The pathophysiology of this condition is intricate and involves multiple molecular and cellular pathways at various levels. This article provides a concise overview of the molecular processes involved in the development of DN. It discusses various factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, cellular damage, autophagy, and epigenetics. The aim is to offer clinicians a valuable reference for DN's diagnosis, treatment, and intervention.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 9","pages":"1240-1253"},"PeriodicalIF":3.3,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Yang, Rong Li, Peijin Wang, Yulan Zhao, Jintao Li, Jianlin Jiao, Hong Zheng
{"title":"Osteoking prevents bone loss and enhances osteoblastic bone formation by modulating the AGEs/IGF-1/β-catenin/OPG pathway in type 2 diabetic db/db mice","authors":"Yi Yang, Rong Li, Peijin Wang, Yulan Zhao, Jintao Li, Jianlin Jiao, Hong Zheng","doi":"10.1002/cbin.12215","DOIUrl":"10.1002/cbin.12215","url":null,"abstract":"<p>Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks in the present treatment. Osteoking (OK) is widely used for treating fractures and femoral head necrosis. However, OK is seldom reported in the field of T2DOP, and its role and mechanism of action need to be elucidated. Consequently, this study investigated whether OK improves bone remodeling and the mechanisms of diabetes-induced injury. We used <i>db/db</i> mice as a T2DOP model and stimulated MC3T3-E1 cells (osteoblast cell line) with high glucose (HG, 50 mM) and advanced glycation end products (AGEs, 100 µg/mL), respectively. The effect of OK on T2DOP was assessed using a combined 3-point mechanical bending test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The effect of OK on enhancing MC3T3-E1 cell differentiation and mineralization under HG and AGEs conditions was assessed by an alkaline phosphatase activity assay and alizarin red S staining. The AGEs/insulin-like growth factor-1(IGF-1)/β-catenin/osteoprotegerin (OPG) pathway-associated protein levels were assayed by western blot analysis and immunohistochemical staining. We found that OK reduced hyperglycemia, attenuated bone damage, repaired bone remodeling, increased tibial and femoral IGF-1, β-catenin, and OPG expression, and decreased receptor activator of nuclear kappa B ligand and receptor activator of nuclear kappa B expression in <i>db/db</i> mice. Moreover, OK promoted the differentiation and mineralization of MC3T3-E1 cells under HG and AGEs conditions, respectively, and regulated the levels of AGEs/IGF-1/β-catenin/OPG pathway-associated proteins. In conclusion, our results suggest that OK may lower blood glucose, alleviate bone damage, and attenuate T2DOP, in part through activation of the AGEs/IGF-1/β-catenin/OPG pathway.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 10","pages":"1507-1519"},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ginsenoside Rb3 alleviates the formation of osteoclasts induced by periodontal ligament fibroblasts in the periodontitis microenvironment through the STAT3 pathway","authors":"Yuhua Zhang, Hanping Shi","doi":"10.1002/cbin.12201","DOIUrl":"10.1002/cbin.12201","url":null,"abstract":"<p>This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti-inflammatory effects of Rb3 on hPLFs stimulated with <i>Porphyromonas gingivalis</i> lipopolysaccharide (<i>P.g</i>-LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs-induced osteoclast formation was assessed by treating human bone marrow-derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate-resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and IL-18) at both gene and protein levels in hPLFs induced by <i>P.g</i>-LPS. Furthermore, conditioned medium from Rb3 plus <i>P.g</i>-LPS treated hPLFs notably decreased the number of TRAP-positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the <i>P.g</i>-LPS-induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in <i>P.g</i>-LPS-stimulated hPLFs and reduces hPLFs-induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 9","pages":"1343-1353"},"PeriodicalIF":3.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corelating the molecular structure of BAG3 to its oncogenic role","authors":"Tabinda Showkat Pattoo, Firdous A. Khanday","doi":"10.1002/cbin.12199","DOIUrl":"10.1002/cbin.12199","url":null,"abstract":"<p>BAG3 is a multifaceted protein characterised by having WW domain, PXXP motif and BAG domain. This protein gets upregulated during malignant transformation of cells and has been associated with poorer survival of patients. Procancerous activity of BAG domain of BAG3 is well documented. BAG domain interacts with ATPase domain of Hsp-70 preventing protein delivery to proteasome. This impediment results in enhanced cell survival, proliferation, resistance to apoptosis and chemoresistance. Besides BAG domain other two domains/motifs of BAG3 are under research vigilance to explore its further oncogenic role. This review summarises the role of different structural determinants of BAG3 in elevating oncogenesis. Based on the already existing findings, more interacting partners of BAG3 are anticipated. The anticipated partners of BAG3 can shed a wealth of information into the mechanistic insights of its proproliferative role. Proper insights into the mechanistic details adopted by BAG3 to curtail/elaborate activity of anticipated interacting partners can serve as a potent target for development of therapeutic interventions.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 8","pages":"1080-1096"},"PeriodicalIF":3.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive analysis of the prognostic value of glutathione S-transferases Mu family members in breast cancer","authors":"Nazanin Gohari, Elham Abbasi, Hassan Akrami","doi":"10.1002/cbin.12195","DOIUrl":"10.1002/cbin.12195","url":null,"abstract":"<p>Breast cancer (BC) remains a significant public health concern globally, with a high number of reported cases and a substantial number of deaths every year. Accumulating reactive oxygen species (ROS) and oxidative stress are related to BC and the Glutathione S-transferases Mu (GSTM) family is one of the most important enzymatic detoxifiers associated with many cancers. In this study, UALCAN, Kaplan-Meier plotter, bc-GenExMiner, cBioPortal, STRING, Enrichr, and TIMER databases were employed to carry out a comprehensive bioinformatic analysis and provide new insight into the prognostic value of GSTMs in BC. <i>GSTM2-5</i> genes in mRNA and protein levels were found to be expressed at lower levels in breast tumors compared to normal tissues, and reduction in mRNA levels is linked to shorter overall survival (OS) and relapse-free survival (RFS). The lower mRNA levels of <i>GSTM</i>s were strongly associated with the worse Scarff-Bloom-Richardson (SBR) grades (<i>p</i> < 0.0001). The mRNA levels of all five <i>GSTM</i>s were substantially higher in estrogen receptor (ER)-positive and progesterone receptor (PR)-positive compared to ER-negative and PR-negative BC patients. As well, when nodal status was compared, <i>GSTM1, GSTM3</i>, and <i>GSTM5</i> were significantly higher in nodal-positive BC patients (<i>p</i> < .01). Furthermore, <i>GSTM4</i> had the most gene alteration (4%) among other family members, and <i>GSTM5</i> showed the strongest correlation with CD4<sup>+</sup> T cells (Cor= .234, <i>p</i> = 2.22e-13). In conclusion, our results suggest that GSTM family members may be helpful as biomarkers for prognosis and as therapeutic targets in BC.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 9","pages":"1313-1325"},"PeriodicalIF":3.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria fission accentuates oxidative stress in hyperglycemia-induced H9c2 cardiomyoblasts in vitro by regulating fatty acid oxidation","authors":"Xiaogang Song, Chongxi Fan, Chao Wei, Wuhan Yu, Jichao Tang, Feng Ma, Yongqing Chen, Bing Wu","doi":"10.1002/cbin.12204","DOIUrl":"10.1002/cbin.12204","url":null,"abstract":"<p>Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA (siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 9","pages":"1378-1391"},"PeriodicalIF":3.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbin.12204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ATAD3 is a limiting factor in mitochondrial biogenesis and adipogenesis of white adipocyte-like 3T3-L1 cells","authors":"Shuijie Li, Rui Xu, Yao Yao, Denis Rousseau","doi":"10.1002/cbin.12206","DOIUrl":"10.1002/cbin.12206","url":null,"abstract":"<p>ATAD3 is a vital ATPase of the inner mitochondrial membrane of pluri-cellular eukaryotes, with largely unknown functions but early required for organism development as necessary for mitochondrial biogenesis. ATAD3 knock-down in <i>C. elegans</i> inhibits at first the development of adipocyte-like intestinal tissue so we used mouse adipocyte model 3T3-L1 cells to analyze ATAD3 functions during adipogenesis and lipogenesis in a mammalian model. ATAD3 function was studied by stable and transient modulation of ATAD3 expression in adipogenesis- induced 3T3-L1 cells using Knock-Down and overexpression strategies, exploring different steps of adipocyte differentiation and lipogenesis. We show that (i) an increase in ATAD3 is preceding differentiation-induced mitochondrial biogenesis; (ii) downregulation of ATAD3 inhibits adipogenesis, lipogenesis, and impedes overexpression of many mitochondrial proteins; (iii) ATAD3 re-expression rescues the phenotype of ATAD3 KD, and (iv) differentiation and lipogenesis are accelerated by ATAD3 overexpression, but inhibited by expression of a dominant-negative mutant. We further show that the ATAD3 KD phenotype is not due to altered insulin signal but involves a limitation of mitochondrial biogenesis linked to Drp1. These results demonstrate that ATAD3 is limiting for in vitro mitochondrial biogenesis and adipogenesis/lipogenesis and therefore that ATAD3 mutation/over- or under-expression could be involved in adipogenic and lipogenic pathologies.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 10","pages":"1473-1489"},"PeriodicalIF":3.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbin.12206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amna Fayyaz, Mahnoor Basit, Andleeb Farooq, Tooba Khan, Umama Ayub, Somia Khan, Muhammad Armaghan, Mati-ur-Rahman, Muhammad Ammad, Dietrich Büsselberg, Khushbukhat Khan, Solomon Habtemariam, Javad Sharifi-Rad
{"title":"Therapeutic potential of ethoxy mansonone G: A comprehensive exploration of its anticancer actions in breast cancer, colorectal cancer, and non-small cell lung carcinoma","authors":"Amna Fayyaz, Mahnoor Basit, Andleeb Farooq, Tooba Khan, Umama Ayub, Somia Khan, Muhammad Armaghan, Mati-ur-Rahman, Muhammad Ammad, Dietrich Büsselberg, Khushbukhat Khan, Solomon Habtemariam, Javad Sharifi-Rad","doi":"10.1002/cbin.12207","DOIUrl":"10.1002/cbin.12207","url":null,"abstract":"<p>Mansonone G (MG), a 1,2-naphthoquinones with antiestrogenic, antimicrobial, and anti-adipogenic activities, is derived from the heartwood of <i>Mansonia gagei</i> Drumm. Ethoxy mansonone G (EMG), an essential derivative of MG, has anticancer and antioxidant agent. EMG also has antiestrogen activity and is demonstrated to lower estrogen receptor expression in endocrine-resistant cells. EMG significantly inhibits cell division, invasion, and anchorage-dependent growth in all cancer types. Through the stimulation of the tumor protein (p53) and extracellular signal-regulated kinase (ERK) signaling cascades, it also causes apoptosis. Moreover, it manifests its anti-cancerous effects in toll-like receptor pathways, c-Jun N-terminal kinase (c-JNK), and nuclear factor kappa B (NF-κB). EMG inhibits the phosphorylation of glycogen synthase kinase (GSK3), Erk, protein kinase B (Akt), and mammalian target of rapamycin (mTOR). By interfering with molecular cascades, EMG significantly reduces the metabolism of cancer cells. This paper focuses on the potential use of EMG in cancer treatment. Moreover, it states the methodology by which specific assays establish the anti-cancerous role of EMG. Breast cancer, non-small cell lung cancer, and colorectal cancer are only a few of the cancers for which EMG was shown to be effective. Through further research, EMG may be developed as a therapeutic solution to complications caused by cancer. This study presents EMG as a novel candidate for cancer therapy, offering a unique combination of pharmacological advantages and mechanistic insights that warrant further exploration and development toward addressing the complexities of cancer treatment.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 9","pages":"1229-1239"},"PeriodicalIF":3.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andreia Maria da Silva, Ana Glória Pereira, Luana Graziele Pereira Bezerra, Andreza Vieira Brasil, Alexsandra Fernandes Pereira, Moacir Franco de Oliveira, Ana Paula Ribeiro Rodrigues, Lucy Vanessa Sulca Ñaupas, Pierre Comizzoli, Alexandre Rodrigues Silva
{"title":"Synergistic effects of glial cell line-derived neurotrophic factor and base-medium on in vitro culture of testicular tissue derived from prepubertal collared peccary","authors":"Andreia Maria da Silva, Ana Glória Pereira, Luana Graziele Pereira Bezerra, Andreza Vieira Brasil, Alexsandra Fernandes Pereira, Moacir Franco de Oliveira, Ana Paula Ribeiro Rodrigues, Lucy Vanessa Sulca Ñaupas, Pierre Comizzoli, Alexandre Rodrigues Silva","doi":"10.1002/cbin.12203","DOIUrl":"10.1002/cbin.12203","url":null,"abstract":"<p>We evaluated the influence of different media plus various concentrations of Glial cell line-derived neurotrophic factor (GDNF) during the in vitro culture (IVC) of testicular tissues from prepubertal collared peccary. Testes from 5 individuals were collected, fragmented and cultured for 28 days (34°C and 5% CO<sub>2</sub>). Culture media were Dulbecco's modified essential medium (DMEM) or stem cell serum free media (StemPro-34™ SFM), both supplemented with various concentrations of GDNF (0, 10, or 20 ng/mL). Fragments were cultured on the flat surface of 0.75% agarose gel and were evaluated every 7 days for fragment area, histomorphology, cellular viability, and proliferative activity. Data were expressed as mean ± standard error and analyzed by Kruskal–Wallis's and Tukey test. Fragments area decreased over the 28 days-culture, regardless of the treatment. For morphology, the StemPro-37 SFM medium plus 10 ng/mL GDNF provided higher scores at all time points in comparison to DMEM using any GDNF concentration (<i>p</i> < .05). After 28 days, similar cellular viability (~70%) was observed in all treatments (<i>p</i> > .05). For proliferating cell nuclear antigen assay, only DMEM plus 10 ng/mL GDNF improved (<i>p</i> < .05) cellular proliferation on Days 14 and 28. Looking at argyrophilic nucleolar organizing regions, after 28 days, there were no differences among treatments regarding cell proliferative capacity for both spermatogonia and Sertoli cells (<i>p</i> > .05). In summary, the DMEM and StemPro-34 SFM are adequate medium for IVC of prepubertal peccary testicular tissue. Supplementation with GDNF, especially at a 10 ng/mL concentration, appears to be essential for the maintenance of cell survival and proliferation.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 9","pages":"1364-1377"},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Surface charge, but not size, of liposomes is involved in the suppression of rat basophilic leukemia (RBL-2H3) cell degranulation mediated by Akt phosphorylation","authors":"Yoshikazu Inoh, Nanami Ito, Satoru Yokawa, Ruriko Suzuki, Tadahide Furuno","doi":"10.1002/cbin.12205","DOIUrl":"10.1002/cbin.12205","url":null,"abstract":"<p>Cationic liposomes composed of cholesteryl-3β-carboxyamidoethylene-<i>N</i>-hydroxyethylamine (OH-chol) and 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphatidylethanolamine (DOPE) inhibit mast cell degranulation mediated via crosslinking of high-affinity IgE receptors (FcεRI). Although the inhibitory efficiency of mast cell degranulation is altered by modifying the ratio of OH-chol and DOPE in cationic liposomes, the manner in which physicochemical properties, such as surface charge and size, influence suppression is not clear. We observed that positive surface charge, but not the size, of liposomes plays a role in suppressing rat basophilic leukemia (RBL-2H3) cell activation. Pretreatment with middle-ratio OH-chol liposomes (zeta potential, 62.2 ± 0.5 mV; diameter, 325.4 ± 7.3 nm) exhibited a larger suppression of RBL-2H3 cell degranulation evoked by FcεRI crosslinking compared with that by low-ratio OH-chol liposomes (zeta potential, 48.6 ± 1.9 mV; diameter, 344.4 ± 25.0 nm), although both liposomes were similarly attached to RBL-2H3 cells. Preparation of middle-ratio OH-chol liposomes, classified roughly by size using an extrusion method, revealed that the liposomal size did not affect the inhibitory efficiency of RBL-2H3 cell activation. Mechanistically, we found that middle-ratio OH-chol liposomes increased the inhibition of antigen-induced Akt phosphorylation compared to low-ratio OH-chol liposomes. We measured the phosphorylation of linker for activation of T cells (LAT) and paxillin, which are important proteins in FcεRI- and focal adhesions (FAs)-mediated signaling, respectively. Middle ratio OH-chol liposomes significantly suppressed antigen-induced paxillin phosphorylation, but did not affect LAT phosphorylation, suggesting that middle-ratio OH-chol liposomes attached to RBL-2H3 cells suppress the degranulation by impairing FA-mediated Akt phosphorylation evoked by FcεRI crosslinking.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 10","pages":"1463-1472"},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}