Life sciences最新文献

{"title":"Transcription factor PRRX1-activated ANXA6 facilitates EGFR-PKCα complex formation and enhances cisplatin sensitivity in bladder cancer","authors":"Jinlong Cao ,&nbsp;Siyu Chen ,&nbsp;Jirong Wang ,&nbsp;Xinpeng Fan ,&nbsp;Shanhui Liu ,&nbsp;Xiaoran Li ,&nbsp;Li Yang","doi":"10.1016/j.lfs.2024.123228","DOIUrl":"10.1016/j.lfs.2024.123228","url":null,"abstract":"<div><h3>Background</h3><div>Tumor resistance to cisplatin represents a major clinical challenge, particularly in bladder cancer (BC). ANXA6 is a member of annexin family, and its role in cisplatin resistance remains unclear. This study explores ANXA6's role in promoting cisplatin sensitivity.</div></div><div><h3>Methods</h3><div>Bioinformatics analyses and clinical specimen verifications assessed the correlation between ANXA6 and cisplatin treatment. A series of assays, including CCK-8, clone formation assay, flow cytometry assays for reactive oxygen species (ROS) and apoptosis, and comet assays, were used to confirm ANXA6's role in enhancing cisplatin sensitivity and re-sensitizing resistant BC cells. Mass spectrometry, immunofluorescence, and co-immunoprecipitation experiments elucidated ANXA6's role in enhancing PKCα/EGFR complex formation and inhibiting the EGFR pathway. ChIP-PCR and dual-luciferase assays determined PRRX1's regulatory role on ANXA6 transcription. Finally, the impact of ANXA6 in vivo was evaluated using xenograft models.</div></div><div><h3>Results</h3><div>Bioinformatics analyses showed a significant correlation between ANXA6 expression and cisplatin sensitivity. In vitro and in vivo experiments confirmed that ANXA6 was a new target for cisplatin treatment. ANXA6 overexpression not only enhanced cell viability inhibition, DNA damage and apoptosis caused by cisplatin, but also re-sensitized cisplatin-resistant cells. Mechanistically, ANXA6 promotes PKCα/EGFR complex formation, inhibiting EGFR phosphorylation and downstream AKT and ERK1/2. Moreover, PRRX1 was identified as a transcription factor promoting ANXA6 expression, thereby augmenting the cytotoxic effects of cisplatin.</div></div><div><h3>Conclusion</h3><div>Our study reveals the mechanism by which ANXA6 enhances cisplatin sensitivity and re-sensitizes resistant cells. The roles of PRRX1 and ANXA6 in cisplatin resistance offer new therapeutic targets to overcome cisplatin resistance in clinical practice.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123228"},"PeriodicalIF":5.2,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycystic ovary syndrome: Recent research and therapeutic advancements","authors":"Shanmugapriya Dilliyappan ,&nbsp;Avanthika Satish Kumar ,&nbsp;Sneha Venkatesalu ,&nbsp;Thirunavukkarasu Palaniyandi ,&nbsp;Gomathy Baskar ,&nbsp;Asha Sivaji ,&nbsp;Safia Obaidur Rab ,&nbsp;Mohd Saeed ,&nbsp;K.S. Shivaranjani","doi":"10.1016/j.lfs.2024.123221","DOIUrl":"10.1016/j.lfs.2024.123221","url":null,"abstract":"<div><div>Polycystic ovary syndrome is often characterized by the appearance of several tiny cysts (fluid-filled sacs) in the ovaries. It is the most significant endocrinopathy affecting 8–13 % of women during their lifetime. Within the dynamic domain of women's health, this syndrome is a widespread issue that presents with an array of signs, including insulin resistance, hirsutism, androgen development, and menstrual flaws prompted by genetic, diet/lifestyle, gut microbiota dysbiosis, and environmental toxins. Impaired folliculogenesis, aberrant cortisol metabolism, and genes associated with steroidogenesis contribute to the pathophysiology of the disease. Moreover, it combines with various concurrent metabolic and idiopathic conditions specifically type 2 diabetes, heart disease, cancer, and infertility. On persuading the reproductive framework of women from ontogeny to menopause, the complexity of the syndrome hereditates generations due to maternal inheritance of hyperandrogenism. The advancement in diagnostic norms paved the way from the Rotterdam criteria to metabolomics, 3D ultrasound, and assisted reproductive technologies. The management and treatment of this hormonal disorder can be prevailed through lifestyle modifications and prompt medications. This review entails the aforementioned benchmarks of the syndrome's complexity and its ongoing research in alleviating its intricate behavioral changes in women from in-utero to menopause.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123221"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tempol mitigates inflammation, oxidative stress, and histopathological alterations of cadmium-induced parotid gland injury in rats","authors":"Samaa Salah Abd El-Fatah ,&nbsp;Ola Elsayed Nafea ,&nbsp;Doaa Mohammed Yousef ,&nbsp;Walaa Samy ,&nbsp;Marwa H.S. Hussien ,&nbsp;Heba M. Arakeep","doi":"10.1016/j.lfs.2024.123233","DOIUrl":"10.1016/j.lfs.2024.123233","url":null,"abstract":"<div><div>Cadmium (Cd) is a potent environmental pollutant that causes functional and structural damage to the salivary glands. Tempol (TEM) has powerful antioxidant activity that can potentially preserve organ function. Aims: This study was designed to investigate the protective effects of TEM on Cd-induced toxicity in rat parotid salivary glands. Materials and methods: Twenty-four adult Wistar male rats were randomly assigned to four equal groups: control, TEM (27.5 g/100 ml), Cd (0.6 g/100 ml), and TEM plus Cd (at the same doses). All treatments were dissolved in distilled water and administered subcutaneously four times a week for four weeks. Parotid gland tissues were isolated and subjected to molecular and histo-biochemical assessments. Key findings: TEM exerted a prophylactic effect against Cd-induced toxicity in the parotid glands by controlling inflammation through the downregulation of toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/ interleukin-1 beta mRNA expression, upregulation of aquaporin-5 mRNA expression, improvement of the oxidant/antioxidant status in the parotid gland, mitigation of endoplasmic reticulum stress, and repair of the associated histological and ultrastructural abnormalities. Significance: TEM protects against Cd-induced toxicity in the parotid glands of rats, attributable at least in part to its anti-inflammatory and antioxidant properties, as well as its ability to inhibit ER stress and facilitate glandular repair. However, the protective effects of TEM did not reach the levels observed in the control group. TEM could be a promising clinical candidate for protecting the salivary glands, particularly in high-risk groups such as workers exposed to Cd and cigarette smokers.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123233"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretoglobin 3A2 peptides have therapeutic potential for allergic airway inflammation","authors":"Reiko Kurotani ,&nbsp;Yui Sato ,&nbsp;Ayaka Okawara ,&nbsp;Nichika Fukuda ,&nbsp;Kengo Hada ,&nbsp;Satoshi Sakahara ,&nbsp;Kei Takakura ,&nbsp;Hiroyuki Abe ,&nbsp;Hiroyuki Konno ,&nbsp;Shioko Kimura","doi":"10.1016/j.lfs.2024.123222","DOIUrl":"10.1016/j.lfs.2024.123222","url":null,"abstract":"<div><div>Three isoforms of secretoglobin (SCGB) 3A2, namely type A, B, and C, are endogenously produced through alternative splicing. SCGB3A2 type A, the correctly spliced major type, begins to be expressed from embryonic day 11.5 in mice and shows various physiological activities such as promoting lung maturation and bronchial branching, anti-inflammatory effects, and ameliorating induced pulmonary fibrosis. To investigate the potential of SCGB3A2 peptides as a therapeutic to treat respiratory diseases, in this study, serially overlapping nine peptides were synthesized to cover the entire type C isoform, and five and one peptides covering the C-terminal region of type A and B, respectively. To evaluate their biological activities, each peptide was subjected to cell proliferation and apoptosis analyses <em>in vitro</em> using mouse lung fibroblast-derived MLg cells, bronchial branching rate using <em>ex vivo</em> mouse fetal lung organ cultures, and <em>in vivo</em> allergic airway inflammation mouse model. Among type A and C peptides, those corresponding to the C-terminal region of the SCGB3A2 sequence exhibited its unique biological activities of promoting cell proliferation and bronchial branching, and/or inhibiting apoptosis. The type B peptide did not show any proliferative effect while inhibited apoptosis. In a mouse model of allergic airway inflammation, lung inflammation was improved by the administration of most of the C-terminal region-derived type A and type C peptides. The results suggest that the bioactivity resides towards the C-terminal region of SCGB3A2 sequence, and the peptides covering this region could be used as a therapeutic in treating lung inflammation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123222"},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative and endoplasmic reticulum stress in diabetes-related hearing loss: Protective effects of thioredoxin","authors":"Meng Xu ,&nbsp;Shiwen Zhong ,&nbsp;Na Zhu ,&nbsp;Sifan Wang ,&nbsp;Jingyi Wang ,&nbsp;Xiang Li ,&nbsp;Xiang Ren ,&nbsp;Hui Kong","doi":"10.1016/j.lfs.2024.123223","DOIUrl":"10.1016/j.lfs.2024.123223","url":null,"abstract":"<div><div>Diabetes mellitus (DM) induces complex physiological changes in the inner ear environment. This study investigates the roles of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in diabetes-related hearing loss (DRHL) and explores the potential of thioredoxin (Trx) in regulating OS, ERS, and apoptosis-related factors to mitigate the progression of hearing impairment. We conducted auditory and serological assessments in 63 patients with type 2 diabetes and 30 healthy controls. Type 2 diabetes models were induced in wild-type and Trx transgenic (Tg) mice, with auditory brainstem response (ABR) used to evaluate hearing changes. Cochlear tissues were isolated to analyse markers of apoptosis, OS, and ERS. Both patients with diabetes and mouse models exhibited hearing loss, alongside increased serum levels of Trx1, TXNIP, and AOPP, indicating oxidative damage. H&amp;E and succinate dehydrogenase (SDH) staining revealed varying degrees of hair cell loss from the base to the apex of the cochlea in diabetic mice, with decreased expression of the hair cell protein prestin gene. Notably, Tg mice showed significant delay in hearing loss progression. In vitro, advanced glycation end-products (AGEs) induced OS and ERS in cochlear-like HEI-OC1 cells, while Trx overexpression enhanced Nrf2 activity, alleviating AGE-induced cellular stress. In conclusion, Trx exhibits protective effects against DRHL, potentially by enhancing Nrf2/HO-1/SOD2 function to reduce OS and ERS.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123223"},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleoylethanolamide mitigates cardiometabolic disruption secondary to obesity induced by high-fat diet in mice","authors":"Federica Comella ,&nbsp;Alana Aragón-Herrera ,&nbsp;Claudio Pirozzi ,&nbsp;Sandra Feijóo-Bandin ,&nbsp;Adriano Lama ,&nbsp;Nicola Opallo ,&nbsp;Stefania Melini ,&nbsp;Filomena Del Piano ,&nbsp;Oreste Gualillo ,&nbsp;Rosaria Meli ,&nbsp;Giuseppina Mattace Raso ,&nbsp;Francisca Lago","doi":"10.1016/j.lfs.2024.123226","DOIUrl":"10.1016/j.lfs.2024.123226","url":null,"abstract":"<div><div>Chronic lipid overnutrition has been demonstrated to promote cardiac dysfunction resulting from metabolic derangement, inflammation, and fibrosis. Oleoylethanolamide (OEA), an endogenous peroxisome proliferator activating receptor (PPAR)-α agonist, has been extensively studied for its metabolic properties.</div><div>The aim of this study was to determine if OEA has beneficial effects on high-fat diet (HFD)-induced cardiac disruption in obese mice, focusing on the underlying pathological mechanisms.</div><div>OEA treatment restores the metabolic pattern, improving serum glycaemic and lipid profile. OEA also reduces heart weight and serum creatine kinase-myocardial band (CK-MB), a marker of cardiac damage. Accordingly, OEA modulates cardiac metabolism, increasing insulin signaling and reducing lipid accumulation. OEA increases AMPK and AKT phosphorylation, converging in the rise of AS160 activation and glucose transporter (GLUT)4 protein level. Moreover, OEA reduces the transcription of the cardiac fatty acid transporter CD36 and fatty acid synthase and increases PPAR-α mRNA levels. Adiponectin and meteorite-like protein transcription levels were significantly reduced by OEA in HFD mice, as well as those of inflammatory cytokines and pro-fibrotic markers. An increased autophagic process was also shown, contributing to OEA's cardioprotective effects. Metabolomic analyses of cardiac tissue revealed the modulation of different lipids, including triglycerides, glycerophospholipids and sphingomyelins by OEA treatment. In vitro experiments on HL-1 cardiomyocytes showed OEA's capability in reducing inflammation and fibrosis following palmitate challenge, demonstrating a direct activity of OEA on cardiac cells, mainly mediated by PPAR-α activation.</div><div>Our results indicate OEA as a potential therapeutic to restrain cardiac damage associated with metabolic disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123226"},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic syndrome promotes resistance to aspirin in mitigating bone loss in murine periodontal disease","authors":"Lucas Sobral de Rossi ,&nbsp;Raquel Pires Nakama ,&nbsp;Lucas Felipe Dos Santos ,&nbsp;Leonardo Berto-Pereira ,&nbsp;Aparecida Donizette Malvezi ,&nbsp;Maria Isabel Lovo-Martins ,&nbsp;Ana Paula Canizares Cardoso ,&nbsp;Luiz Claúdio Tozoni-Filho ,&nbsp;Eduardo Inocente Jussiani ,&nbsp;Andressa Mendes Dionísio de Freitas ,&nbsp;Marli Cardoso Martins-Pinge ,&nbsp;Phileno Pinge-Filho","doi":"10.1016/j.lfs.2024.123224","DOIUrl":"10.1016/j.lfs.2024.123224","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to investigate the protective effects of aspirin (ASA) on alveolar bone loss in a mouse model with metabolic syndrome (MetS) and concurrent periodontal disease (PD). Specifically, the study sought to determine whether ASA could mitigate bone loss in MetS and non-MetS animals with PD and explore the correlation between gingival nitric oxide (NO) levels and bone resorption.</div></div><div><h3>Main methods</h3><div>Newborn female Swiss mice were administered monosodium glutamate (MSG) (4 mg/g) during the initial 5 days of life to induce MetS (MetS group), while the control group (SAL) was administered saline. On the 60th day, PD was induced in both groups. Half of the animals were treated daily with ASA (40 mg/kg). MetS was characterized by the Lee index, blood glucose, and cardiovascular parameters. Maxillae were evaluated by microtomography and histopathology, showing significant bone loss after PD induction.</div></div><div><h3>Key findings</h3><div>Animals with MetS exhibited higher alveolar bone loss than controls. SAL animals treated with ASA had less bone loss than their MetS counterparts. Gingival NO levels were elevated in animals with PD, and a strong correlation was found between NO levels and bone resorption. ASA reduced NO in non-MetS animals, but MetS animals were resistant to this effect.</div></div><div><h3>Significance</h3><div>These findings suggest a protective mechanism of ASA against bone loss in non-MetS animals with PD, an effect that was not observed in MetS animals. Consequently, this study provides novel insights into the intricate relationship between MetS and PD in mice.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123224"},"PeriodicalIF":5.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defects of WFS1-mediated peptide hormones secretion contribute to the manifestations of Wolfram syndrome","authors":"Suli Li ,&nbsp;Linlin Wang ,&nbsp;Yunfei Li ,&nbsp;Liqiao Hu ,&nbsp;Yanying Guo ,&nbsp;Zonghong Li","doi":"10.1016/j.lfs.2024.123219","DOIUrl":"10.1016/j.lfs.2024.123219","url":null,"abstract":"<div><h3>Aims</h3><div>The study aims to investigate whether WFS1 is involved in the regulation of the exportation and secretion of other peptide hormones, as well as to elucidate the precise molecular mechanisms underlying WS caused by pathogenic mutations in the <em>WFS1</em> gene.</div></div><div><h3>Materials and methods</h3><div>The plasma proteome from the WS patients (n = 2, male) and WFS1-deficient mice (n = 5, male) were analyzed using liquid-chromatography tandem mass spectrometry (LC-MS<em>/</em>MS), while age- and gender-matched healthy individuals and wildtype (WT) mice serve as controls. WFS1-deficient mice were intraperitoneally injected with IGF1 starting from 4 weeks of age. Body weight was monitored every 2 days, fasting blood glucose and glucose tolerance test were performed on the day 30 and day 40 after injection of IGF1, respectively. BiFC (bimolecular fluorescence complementation) and Co-immunoprecipitation (IP) were used to analyze the interaction between WFS1 and peptide hormones. Confocal microscopy was employed to analyze the colocalization of IGF1 with ER and Golgi.</div></div><div><h3>Key findings</h3><div>Peptide hormones are deficient in both the plasma of WS patients and WFS1-deficient mice. WFS1 binds to and mediates the secretion of these peptide hormones, suggesting that WFS1 serves as a general COPII vesicular receptor for sorting peptide hormones. Interestingly, the WFS1 pathogenic mutations significantly disrupt its interaction with these peptide hormones. Furthermore, intraperitoneal administration of IGF1 partially attenuates high blood glucose levels in WFS1-deficient male mice.</div></div><div><h3>Significance</h3><div>This study suggests that WS is characterized by defective peptide hormone secretion and proposes administration of these deficient peptide hormones as a promising treatment regimen for WS.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123219"},"PeriodicalIF":5.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation-induced senescence in glioblastoma: An overview of the mechanisms and eradication strategies","authors":"Neda Dehghan ,&nbsp;Seyedeh Nasibeh Mousavikia ,&nbsp;Younes Qasempour ,&nbsp;Hosein Azimian","doi":"10.1016/j.lfs.2024.123218","DOIUrl":"10.1016/j.lfs.2024.123218","url":null,"abstract":"<div><div>Radiotherapy as a treatment method for glioblastoma is limited due to the intrinsic apoptosis resistance mechanisms of the tumor. Administration of higher radiation doses contributes to toxicities in normal tissues and organs at risk, like optic chiasma. Cellular senescence represents an alternative mechanism to apoptosis following radiotherapy in glioblastoma, occurring in both normal and neoplastic cells. Although it impedes the growth of tumors and sustains cells in their cycle, it can also act as a cause of tumor development and recurrence following treatment. In this review, we discuss detailed insights into the significance of radiation-induced senescence in glioblastoma and the underlying mechanisms that lead to radioresistance. We also discuss senescence biomarkers and the role of senescence-associated secretory phenotype (SASP) in tumor recurrence. Finally, we review the studies that have administered potential interventions to eradicate or inhibit senescent cells in glioblastoma after treatment with radiation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123218"},"PeriodicalIF":5.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosiglitazone-induced white adipocyte browning is regulated by actin and Myh9","authors":"Lupeng Chen ,&nbsp;Jingjie Hao ,&nbsp;Junzhi Zhang ,&nbsp;Jian Wu ,&nbsp;Zhuqing Ren","doi":"10.1016/j.lfs.2024.123217","DOIUrl":"10.1016/j.lfs.2024.123217","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigates the role of actin polymerization and Myh9 in mediating lipid droplet (LD) fission during rosiglitazone-induced browning of white adipocytes. The aim is to understand how LD splitting might contribute to the beige conversion of white adipose tissue, providing insights into adipocyte plasticity and metabolic regulation.</div></div><div><h3>Materials and methods</h3><div>C3H10 T1/2-differentiated adipocytes were used as a classical model to study white adipocyte browning. Rosiglitazone was applied to induce browning, and the interactions between LDs and actin, as well as the distribution of Myh9, were assessed using immunofluorescence and Western blotting. In vivo, we employed a microfilament inhibitor to block actin polymerization in cold-stimulated mice and evaluated changes in LD morphology and browning. Furthermore, dynamic live-cell imaging using confocal microscopy was conducted to observe the real-time behavior of LDs during the browning process and to determine whether they undergo fission.</div></div><div><h3>Main findings</h3><div>Our results demonstrate that rosiglitazone significantly induces LD size reduction, a process correlated with the increased contact of LDs with microfilaments. Inhibition of actin polymerization prevented both the reduction in LD size and the browning of white adipocytes, indicating that actin plays a critical role. Myh9 was enriched at the LD fission sites, forming a structure resembling a contractile ring. Overexpression of Myh9 promoted the shrinkage of LD, suggesting that it may be involved in LD fission.</div></div><div><h3>Significance</h3><div>This study identifies actin and Myh9 as key regulators of LD fission in rosiglitazone-induced browning of white adipocytes, offering new insights into the cellular mechanisms of adipocyte plasticity. The findings propose a novel pathway by which LD dynamics contribute to the beige conversion of white fat, with potential implications for metabolic disease therapies targeting adipocyte function and energy expenditure.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123217"},"PeriodicalIF":5.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}