Archives of biochemistry and biophysics最新文献

{"title":"Schizosaccharomyces pombe Grx4 is subject to autophagic degradation under nitrogen- and iron- starvation and ER-stress","authors":"Rong Li,&nbsp;Ying Huang","doi":"10.1016/j.abb.2024.110227","DOIUrl":"10.1016/j.abb.2024.110227","url":null,"abstract":"<div><div>Glutaredoxins (Grxs) are small, heat-stable proteins that serve as multi-functional glutathione （GSH）-dependent thiol transferases. Recent studies have elucidated their role in regulating cellular iron and copper homeostases. In <em>Schizosaccharomyces pombe</em>, five Grxs (Grx1-5) have been identified. Among them， Grx4 and its homologs possess a C-terminal glutaredoxin domain (GRX) and an N-terminal thioredoxin-like domain (TRX). The functional roles of the GRX and TRX domains in Grx4 were investigated by constructing strains that express a truncated Grx4 under the regulation of either a constitutive <em>cam1</em> promoter or its native promoter. Our findings indicated that two autophagy-related (Atg) protein 8 (Atg8)-interacting motifs (AIM), FLKI and FQEI, in the TRX domain of Grx4 are sufficient to induce autophagic degradation under nitrogen- and iron-starvation, respectively. Moreover, the expression level of a vacuolar ferrous iron transporter Pcl1 was altered in Δ<em>atg5</em> or Δ<em>atg8</em> strains under iron starvation,suggesting that autophagy is required for maintaining iron homeostasis in <em>S. pombe</em>. Further investigations revealed that Grx4 is required for cellular survival and endoplasmic reticulum (ER) autophagy (ER-phagy) during dithiothreitol (DTT) treatment, implying a potential correlation between Grxs and ER-stress. Additionally, loss of Grx4 disrupts nuclear integrity during ER stress, highlighting the versatility and importance of further investigations into the functions of Grx4.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110227"},"PeriodicalIF":3.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738227","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":"Engineering of LOV-domains for their use as protein tags","authors":"Saniye G. Kaya ,&nbsp;Andrej Hovan ,&nbsp;Marco W. Fraaije","doi":"10.1016/j.abb.2024.110228","DOIUrl":"10.1016/j.abb.2024.110228","url":null,"abstract":"<div><div>Light-Oxygen-Voltage (LOV) domains are the protein-based light switches used in nature to trigger and regulate various processes. They allow light signals to be converted into metabolic signaling cascades. Various LOV-domain proteins have been characterized in the last few decades and have been used to develop light-sensitive tools in cell biology research. LOV-based applications exploit the light-driven regulation of effector elements to activate signaling pathways, activate genes, or locate proteins within cells. A relatively new application of an engineered small LOV-domain protein called miniSOG (mini singlet oxygen generator) is based on the light-induced formation of reactive oxygen species (ROS). The first miniSOG was engineered from a LOV domain from <em>Arabidopsis thaliana</em>. This engineered 14 kDa light-responsive flavin-containing protein can be exploited as protein tag for the light-triggered localized production of ROS. Such tunable ROS production by miniSOG or similarly redesigned LOV-domains can be of use in studies focused on subcellular phenomena but may also allow new light-fueled catalytic processes. This review provides an overview of the discovery of LOV domains and their development into tools for cell biology. It also highlights recent advancements in engineering LOV domains for various biotechnological applications and cell biology studies.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110228"},"PeriodicalIF":3.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723766","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":"Targeting inhibition of T3JAM reduces brain cell ferroptosis in rat following ischemia/reperfusion via a mechanism involving prevention of TLR4-mediated iron overload","authors":"Qing Li ,&nbsp;Yi-Yue Zhang ,&nbsp;Dan Peng ,&nbsp;Hong-Rui Liu ,&nbsp;Lin Wu ,&nbsp;Ting-Ting Tang ,&nbsp;Xiu-Ju Luo","doi":"10.1016/j.abb.2024.110225","DOIUrl":"10.1016/j.abb.2024.110225","url":null,"abstract":"<div><div>Iron overload-dependent ferroptosis is believed to contribute to the brain injury of ischemia/reperfusion (I/R), whereas toll-like receptor 4 (TLR4) can exert pro-ferroptosis effect via inhibiting the glutathione peroxidase 4 (GPX4) level, but the mechanisms behind these phenomenon are not fully elucidated. Tumor necrosis factor receptor correlated factor 3-interaction Jun amino-terminal kinase [JNK]-activating modulator (T3JAM) can activate specific molecule and its downstream signaling pathways, including TLR4. This study aims to explore whether targeting T3JAM can reduce I/R-induced ferroptosis in brain via downregulating TLR4. A Sprague Dawley (SD) rat model of cerebral I/R injury was established by 2 h-ischemia plus 24 h-reperfusion, which displayed brain injury (increases in neurological deficit score and infarct volume) and upregulation of T3JAM and TLR4, concomitant with the increased ferroptosis, reflected by increases in the levels of transferrin receptor protein 1 (TfR1), total iron, Fe²⁺ and lipid peroxidation (LPO) while decreases in the levels of ferroportin (FPN) and GPX4. Consistently, similar results were achieved in the cultured HT22 cells subjected to 8h-oxygen-glucose deprivation plus 12 h-reoxygenation (OGD/R), and knockdown of T3JAM reversed these phenomena. Moreover, Telaprevir, an anti-hepatitis C virus (HCV) drug, could also provide beneficial effect on alleviating ischemic brain injury via inhibition of T3JAM. Based on these observations, we conclud that inhibition of T3JAM can reduce I/R-induced brain cell ferroptosis through downregulating TLR4 and that T3JAM could be a potential target for identifying novel or existing drugs (such as Telaprevir) to treat cerebral I/R injury.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110225"},"PeriodicalIF":3.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708521","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":"Epigallocatechin-3-gallate inhibit the protein arginine methyltransferase 5 and enhancer of Zeste homolog 2 in breast cancer both in vitro and in vivo","authors":"Kirankumar Nalla ,&nbsp;Biji Chatterjee ,&nbsp;Jagadeesha Poyya ,&nbsp;Aishwarya Swain ,&nbsp;Krishna Ghosh ,&nbsp;Archana Pan ,&nbsp;Chandrashekhar G. Joshi ,&nbsp;Bramanandam Manavathi ,&nbsp;Santosh R. Kanade","doi":"10.1016/j.abb.2024.110223","DOIUrl":"10.1016/j.abb.2024.110223","url":null,"abstract":"<div><h3>Purpose</h3><div>Histone methyltransferases are enzymes that selectively methylate lysine or arginine residues on both histone and non-histone proteins, categorized into lysine methyltransferases and arginine methyltransferases. Notably, EZH2 and PRMT5 are known for catalyzing trimethylation of H3 at K27 and symmetric dimethylation of H4 at R3, respectively. These methylation events are recognized as characteristic histone-repressive marks in cancer. The over expression of PRMT5 and EZH2 were reported in various cancers and recognized as a drug target. The study aims to explore the inhibitory potential of phytocompound, Epigallocatechin-3-gallate (EGCG), against PRMT5 and EZH2 in the breast cancer model.</div></div><div><h3>Methods</h3><div>Screening of an array of phytocompounds was conducted through a combination of <em>in-silico</em> and <em>in-vitro</em> assays. Interactions between EGCG and human PRMT5: MEP50 and EZH2 were evaluated using molecular docking. Binding efficiency was validated, by Surface Plasmon Resonance studies and inhibitory potential was accessed by <em>in vitro</em> methylation followed by western blots, ELISA, and cell-based assays. <em>In-vivo</em> efficacy of EGCG was carried on cell line derived mice xenograft model.</div></div><div><h3>Results</h3><div>EGCG demonstrated robust interactions with PRMT5:MEP50 complex and EZH2, particularly within the SAM binding site. Surface Plasmon Resonance analysis revealed strong binding affinity in nanomolar concentrations, particularly with PRMT5-MEP50 compared to EZH2. <em>In-vitro</em> assays confirmed EGCG's ability to inhibit PRMT5 and EZH2, leading to a decrease in their catalytic products, namely H4R3me2s and H3K27me3, respectively. EGCG treatment induced both autophagy and apoptosis <em>invitro</em>. <em>In-vivo</em> studies demonstrated significant reductions in tumor size and the proliferation marker ki67, accompanied by a decrease in histone repressive marks.</div></div><div><h3>Conclusion</h3><div>The findings suggest that EGCG effectively inhibits PRMT5 and EZH2, underscoring its potential for combined therapeutic strategies in cancer treatment.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110223"},"PeriodicalIF":3.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709018","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":"Structural and biochemical analyses reveal quinic acid inhibits DAHP synthase a key player in shikimate pathway","authors":"Kuldeep Jangid,&nbsp;Jai Krishna Mahto,&nbsp;K Amith Kumar,&nbsp;Preeti Dhaka,&nbsp;Anchal Sharma,&nbsp;Amaan Tariq,&nbsp;Ashwani Kumar Sharma,&nbsp;Pravindra Kumar","doi":"10.1016/j.abb.2024.110219","DOIUrl":"10.1016/j.abb.2024.110219","url":null,"abstract":"<div><div>The shikimate pathway, essential for aromatic amino acid biosynthesis, is absent in animals, making its enzymes promising targets for developing antimicrobials. 3-Deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) catalyzes the first committed step, which serves as the primary checkpoint for regulating the flow within the pathway, regulated by its end products (Phe, Tyr and Trp). Previously, we identified chlorogenic acid (CGA), an ester of caffeic and quinic acid, as an inhibitor of DAHPS from <em>Bacillus subtilis,</em> prompting us to investigate quinic acid as a potential inhibitor of <em>Providencia alcalifaciens</em> DAHPS (<em>Pa</em>DAHPS). Here, we report the crystal structures of phenylalanine-sensitive DAHPS from <em>P</em><em>rovidencia</em> <em>alcalifaciens</em> in complex with phenylalanine (Phe) and quinic acid (QA) at resolutions of 2.5 Å and 2.68 Å, respectively. Structural analysis reveals that QA binds to the same site as Phe, with biophysical assays showing a similar binding affinity (<em>K</em>_<em>D</em> = 42 μM for QA and <em>K</em>_<em>D</em> = 32 μM for Phe). <em>In vitro</em> inhibition studies demonstrated that QA and Phe inhibit <em>Pa</em>DAHPS activity, with ^app<em>K</em>_<em>i</em> values of 382 μM and 132 μM, respectively. Additionally, QA inhibited the growth of several bacterial species, including <em>Pseudomonas aeruginosa, Moraxella catarrhalis, Providencia alcalifaciens, Staphylococcus aureus, Escherichia coli</em> with minimum inhibitory concentrations (MICs) ranging from 2.5 to 5 mg/ml. These findings identify quinic acid as a promising scaffold for developing novel antimicrobial agents targeting the shikimate pathway, providing potential therapeutic strategies for bacterial infections.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110219"},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680679","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":"OAS1 induces endothelial dysfunction and promotes monocyte adhesion through the NFκB pathway in atherosclerosis","authors":"Miao Liang ,&nbsp;Wei-Kang Li ,&nbsp;Xi-Xi Xie ,&nbsp;Bai-Cong Lai ,&nbsp;Jing-Jing Zhao ,&nbsp;Ke-Wei Yu ,&nbsp;Pei-Feng Ke ,&nbsp;Yun-Xiu Wang ,&nbsp;Chun-Min Kang ,&nbsp;Xian-Zhang Huang","doi":"10.1016/j.abb.2024.110222","DOIUrl":"10.1016/j.abb.2024.110222","url":null,"abstract":"<div><div>Cardiovascular disease is characterized by chronic inflammation and atherosclerosis (AS) is the pathological basis. Mitigating endothelial dysfunction and mononuclear cell adhesion is a crucial approach in impeding the initial advancement of AS. As an inflammation-immune regulation-related protein, 2′-5′-oligoadenylate synthetase 1 (OAS1) plays a critical role in inflammation, but its impact on endothelial dysfunction and mononuclear cell adhesion is not well understood. In this study, bioinformatic analysis revealed a significant enrichment of OAS1 in atherosclerotic plaques within human aortic sections. In addition, OAS1 was detected in atherosclerotic plaques within human aortic sections across various stages of development, with elevated expression observed in more advanced plaques. The expression of OAS1 exhibited a distinct temporal and concentration-dependent upregulation in response to lipopolysaccharide (LPS) stimulation. Notably, the deficiency of OAS1 markedly attenuated the elevation in reactive oxygen species (ROS) levels, nitric oxide (NO) concentrations, and monocyte adhesion induced by LPS. A positive correlation was observed between the levels of NFκBp65 and OAS1 in human plaques, and the deletion of OAS1 led to a down-regulation of P65 expression. Furthermore, the simultaneous knockdown of OAS1 and NFκBp65 resulted in a significant amelioration of endothelial dysfunction (including ROS, NO, and inflammation factors) and monocyte adhesion, suggesting a synergistic interaction between OAS1 and NFκBp65. These findings underscore the potential of OAS1 to modulate the extent of endothelial dysfunction and monocyte adhesion through its regulation of NFκBp65 thereby positioning it as a promising therapeutic target for the management of AS.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110222"},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685773","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":"The effect of acute hypoxic exercise on the protein kinase A/ arachidonic acid/ transient receptor potential vanilloid 4 pathway in the prefrontal cortex of rats","authors":"Wenlei Xu,&nbsp;Xing Huang,&nbsp;Xiaolong Wu","doi":"10.1016/j.abb.2024.110214","DOIUrl":"10.1016/j.abb.2024.110214","url":null,"abstract":"<div><div>Acute hypoxic exercise will cause insufficient oxygen supply in brain tissue, and a succession of variations such as central dysfunction will occur. For example, the muscles don't have an adequate supply of oxygen, which leads to decrease in exercise capacity (Imray et al., 2005) [1]. The prefrontal cortex in the brain is primarily responsible for regulating the executive functions of the brain. TRPV4 channel is a cation channel with permeability to Ca²⁺. Signals such as hypotonic solution stimulation, cell swelling, temperature stimulation, mechanical stimulation, arachidonic acid and its metabolites can activate TRPV4 channel.</div></div><div><h3>Purpose</h3><div>In conditions of ischemia and hypoxia, the central nervous system of the brain is damaged. Therefore, studying the biological mechanism of TRPV4 pathway can help prevent the damage caused by cerebral ischemia and hypoxia to the human.</div></div><div><h3>Results</h3><div>Studies have found that PKA-mediated phosphorylation at Ser-824 affects AA. This is an important signaling pathway for coronary dilatation. This signaling pathway can activate TRPV4 channels. Therefore, we studied the effect of acute hypoxic exercise on the PKA/AA/TRPV4 pathway in the prefrontal cortex of rats. Furthermore, we concluded that the hypoxic environment can shorten the time of increasing load exercise in rats. In this way, the rat entered a state of exhaustion in advance, and the exercise ability was significantly reduced. After further study, blocking TRPV4 channel can prolong the time of incremental load exercise in hypoxic environment, and the exercise ability is improved. Acute hypoxic exercise led to an increase in the concentration of 14,15-EET, which was speculated to be one of the reasons for the increased expression of TRPV4 channels. Acute hypoxic exercise can activate the PKA/AA/TRPV4 signaling pathway in the prefrontal cortex of rats. Further research on blocking the TRPV4 channel can alleviate the activation of the PKA/AA/TRPV4 signaling pathway in the prefrontal cortex of rats by acute hypoxic exercise.</div></div><div><h3>Conclusion</h3><div>These results suggest that blocking the TRPV4 channel may be one of the ways to reduce the damage and apoptosis of prefrontal cortex cells in rats due to acute hypoxic exercise. In future studies, multiple time points will be selected for collection. Alternatively, TRPV4 agonists, PKA agonists or blockers and 14,15-EET agonists or blockers can be added for further pathway validation. To provide a biological mechanism for the study of nutrient targets on the problem of reduced exercise capacity when military personnel and travel enthusiasts first went to the plateau. Better medical reference for athletes training at high altitudes or patients with respiratory issues.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110214"},"PeriodicalIF":3.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680680","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":"ECH 1 attenuates atherosclerosis by reducing macrophage infiltration and improving plaque stability through CD36 degradation","authors":"Caijun Rao ,&nbsp;Haojie Qin ,&nbsp;Zhipeng Du","doi":"10.1016/j.abb.2024.110217","DOIUrl":"10.1016/j.abb.2024.110217","url":null,"abstract":"<div><div>Enoyl coenzyme A hydratase 1 (ECH1) is a secreted protein implicated in numerous metabolic disorders, yet its role in the pathogenesis of atherosclerosis remains unclear. In this study, we found higher serum ECH1 levels in coronary artery disease (CAD) patients and apolipoprotein E (ApoE)^−/− mice on a western diet for 12 weeks. In vivo, aorta and aortic sinus histological staining revealed that intraperitoneal injection of recombinant ECH1 reduced aortic lesions, inflammation, and macrophage infiltration in ApoE^−/− mice. In vitro, incubating peritoneal macrophages with recombinant ECH1 protein reduced oxidized low-density lipoprotein uptake and increased macrophage migration. Mechanically, we observed that recombinant ECH1 incubation led to a reduction in the protein levels of scavenger receptor cluster of differentiation 36 (CD36) in primary macrophages through the promotion of CD36 protein degradation. Additionally, we found that chloroquine (CQ), a lysosomal inhibitor, mitigated this pro-degradation effect. Taken together, our findings provide unique evidence that ECH1 can attenuate the severity of atherosclerotic plaques, especially improving the stability of plaques, by decreasing macrophage infiltration. ECH1 demonstrates its protective effect by enhancing the lysosome-dependent degradation of CD36, suggesting its potential as a viable target for the prevention and treatment of atherosclerosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"763 ","pages":"Article 110217"},"PeriodicalIF":3.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646050","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":"Effects of sulforaphane on prostate cancer stem cells-like properties: In vitro and molecular docking studies","authors":"Yanling Xuan ,&nbsp;Jingyi Xu ,&nbsp;Hongliang Que ,&nbsp;Jianyun Zhu","doi":"10.1016/j.abb.2024.110216","DOIUrl":"10.1016/j.abb.2024.110216","url":null,"abstract":"<div><div>The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. A critical factor contributing to its incidence and development is the presence of prostate cancer stem cells (PCSCs). Targeting PCSCs has become key in enhancing therapeutic and clinical outcomes of prostate cancer. Sulforaphane (SFN), a compound found in cruciferous vegetables, has shown effective antineoplastic activity in prostate cancer. Yet, its mechanisms of action in PCSCs remains unclear. In the present study, tumorsphere formation assay was used to isolate and enrich PCSCs from PC-3 cells. Our results found that SFN effectively reduced the activity of PCSCs, including the ability of tumorsphere formation, the number of CD133 positive cells, and the expression of PCSCs markers. Moreover, the data showed that SFN inhibited PCSCs through downregulating the activation of Wnt/β-catenin and hedgehog signaling pathways in PCSCs. Furthermore, the verification experiments showed that the activators of Wnt/β-catenin (LiCl) and hedgehog (purmorphamine) attenuated the effects of SFN on PCSCs, including the expression of stem cell markers, cell proliferation and apoptosis. Meanwhile, suppression of β-catenin or Smoothened enhanced the effects of SFN on PCSCs. In addition, molecular docking further indicated that SFN inhibited Wnt/β-catenin and hedgehog pathways by directly targeting β-catenin and Smoothened. Taken together, our results demonstrated that SFN targeted PCSCs through Wnt/β-catenin and hedgehog pathways to inhibit stemness and proliferation and induce apoptosis. Findings from this study could provide new insights into SFN as a dietary supplement or adjunct to chemotherapy.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110216"},"PeriodicalIF":3.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643275","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":"Tanshinone IIA alleviates inflammation-induced skeletal muscle atrophy by regulating mitochondrial dysfunction","authors":"Dong Han ,&nbsp;Yun-Biao Chen ,&nbsp;Kai Zhao ,&nbsp;Hong-Zhou Li ,&nbsp;Xing-Yu Chen ,&nbsp;Guo-Zheng Zhu ,&nbsp;Chen Tu ,&nbsp;Jia-Wen Gao ,&nbsp;Jing-Shen Zhuang ,&nbsp;Zhi-Yong Wu ,&nbsp;Zhao-Ming Zhong","doi":"10.1016/j.abb.2024.110215","DOIUrl":"10.1016/j.abb.2024.110215","url":null,"abstract":"<div><div>Skeletal muscle atrophy, characterized by loss of muscle mass and function, is often linked to systemic inflammation. Tanshinone IIA (Tan IIA), a major active constituent of <em>Salvia miltiorrhiza</em>, has anti-inflammatory and antioxidant properties. However, the effect of Tan IIA on inflammation-induced skeletal muscle atrophy remains unclear. Here, a mice model of the inflammatory muscle atrophy was established using lipopolysaccharide (LPS). Tan IIA intervention significantly increased muscle mass and strength, improved muscle fiber size, and maintained the integrity of skeletal muscle mitochondrial morphology in LPS-treated mice. Myotubes derived from myosatellite cells (MUSCs) were exposed to LPS in vitro<em>.</em> Tan IIA treatment inhibited LPS-induced muscle protein degradation and increased myotube diameter. Notably, Tan IIA attenuated LPS-induced inflammatory response and hyperactive mitophagy both in vivo and in vitro. In addition, Tan IIA treatment effectively diminished oxidative stress, inhibited the accumulation of mitochondrial reactive oxygen species (mtROS), and attenuated mitochondrial fission in LPS-treated myotubes. Reducing mtROS production helped to inhibit LPS-induced excessive mitophagy and myotubes atrophy. Together, our results reveal that Tan IIA can protect against inflammation-induced skeletal muscle atrophy by regulating mitochondrial dysfunction, presenting innovative potential therapeutics for skeletal muscle atrophy.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110215"},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638205","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}