Archives of biochemistry and biophysics最新文献

筛选
英文 中文
Critical aggregation concentration and reversibility of amyloid-β (1–40) oligomers 淀粉样蛋白-β(1-40)寡聚体的临界聚集浓度和可逆性。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-10 DOI: 10.1016/j.abb.2024.110179
{"title":"Critical aggregation concentration and reversibility of amyloid-β (1–40) oligomers","authors":"","doi":"10.1016/j.abb.2024.110179","DOIUrl":"10.1016/j.abb.2024.110179","url":null,"abstract":"<div><div>Amyloid-beta (Aβ) aggregation is a critical factor in the pathogenesis of Alzheimer's disease, with distinct aggregation behaviours observed between its isoforms Amyloid-β 1–40 (Aβ40) and 1–42 (Aβ42). In this study, we investigated the aggregation properties of Aβ40 using fluorescence correlation spectroscopy (FCS) and detailed data analysis. Our results reveal that Aβ40 undergoes a two-step cooperative aggregation process. The first step, characterized by a critical aggregation concentration (<em>cac</em>) of 0.5 ± 0.3 μM, results in the formation of metastable oligomers of 5–25 monomers and stable oligomers of 50–100 monomers, with less than 10 % of the total amyloid aggregated. The second step, with a <em>cac</em> of 19 ± 2 μM, leads to the formation of much larger aggregates, consistent with protofibrils, and approximately 50 % aggregated amyloid. Notably, the <em>cac</em> for Aβ40 is significantly higher, and the fraction of aggregated amyloid is much lower compared to Aβ42, indicating a lower propensity for aggregation. Additionally, our findings suggest that Aβ40 early oligomers are reversible upon dilution, albeit with a kinetic barrier to disaggregation. These insights into the aggregation mechanisms of Aβ40 enhance our understanding of its role in Alzheimer's disease and may inform therapeutic strategies targeting amyloid aggregation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405963","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}
引用次数: 0
Folic acid-functionalized and acetyl-terminated dendrimers as nanovectors for co-delivery of sorafenib and 5-fluorouracil 叶酸官能化和乙酰基端树枝状聚合物作为共同递送索拉非尼和 5-氟尿嘧啶的纳米载体。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-10 DOI: 10.1016/j.abb.2024.110176
{"title":"Folic acid-functionalized and acetyl-terminated dendrimers as nanovectors for co-delivery of sorafenib and 5-fluorouracil","authors":"","doi":"10.1016/j.abb.2024.110176","DOIUrl":"10.1016/j.abb.2024.110176","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Molecular dynamics (MD) simulations were employed to investigate the simultaneous association of sorafenib (SF) and 5-fluorouracil (5-FU) with generation 4 (G4) acetyl-terminated poly(amidoamine) (PAMAM) dendrimers conjugated with folic acid (G4ACE-FA). Simulations were conducted under physiological (pH 7.4) and acidic (pH &lt; 5) conditions, representing the environments of healthy and cancerous cells, respectively. The average radius of gyration (&lt;em&gt;R&lt;/em&gt;&lt;sub&gt;g&lt;/sub&gt;) of G4ACE-FA was determined to be approximately 1.85 ± 0.01 nm and 2.31 ± 0.03 nm under physiological and acidic conditions, respectively. Drug loading did not exert a significant influence on the size and conformational compactness of G4ACE-FA at both neutral and low pH. However, a discernible increase in dendrimer size was observed upon simultaneous encapsulation and/or conjugation of both drug molecules. The relaxation times of G4ACE-FA were calculated to be 10.2 ns and 9.6 ns at neutral and low pH, respectively, indicating comparable equilibrium rates under both pH environments. The incorporation of small 5-FU molecules did not demonstrably alter the dendrimer's microstructure. The observed doubling of the relaxation time under acidic conditions can be attributed to the relatively compact structure of the dendrimer at neutral pH and the continuous intrastructural rearrangements occurring at acidic pH. The prolonged relaxation time observed in the G4ACE-FA:5-FU:SF complex is attributed to competitive interactions between 5-FU and SF molecules during simultaneous encapsulation by the dendrimer. Analysis of the unloaded and loaded structures of G4ACE-FA under varying pH conditions revealed a densely packed conformation at neutral pH and a more open, sponge-like structure at low pH. The solvent-accessible surface area (SASA) of the dendrimer was assessed at both pH conditions. At neutral pH, SASA values were approximately 124.0 ± 2.8 nm&lt;sup&gt;2&lt;/sup&gt;, 127.5 ± 2.6 nm&lt;sup&gt;2&lt;/sup&gt;, 131.3 ± 2.6 nm&lt;sup&gt;2&lt;/sup&gt;, and 133.3 ± 2.6 nm&lt;sup&gt;2&lt;/sup&gt; for unloaded G4ACE-FA and the G4ACE-FA:5-FU, G4ACE-FA:SF, and G4ACE-FA:5-FU:SF complexes, respectively. Drug incorporation had a minimal effect on SASA at neutral pH. At low pH, the corresponding values were 198.2 ± 4.7 nm&lt;sup&gt;2&lt;/sup&gt;, 195.8 ± 4.8 nm&lt;sup&gt;2&lt;/sup&gt;, 212.5 ± 6.1 nm&lt;sup&gt;2&lt;/sup&gt;, and 215.4 ± 4.2 nm&lt;sup&gt;2&lt;/sup&gt;. These findings suggest that 5-FU encapsulation resulted in minimal changes to the dendrimer's surface exposure to the solvent, potentially due to its small size. In contrast, SF interaction led to a more pronounced increase in SASA, indicating structural expansion to accommodate SF conjugation. The equilibrium stoichiometry of the G4ACE-FA:5-FU complex was determined to be 1:11 and 1:3 at neutral and low pH, respectively. Similarly, the G4ACE-FA:SF complex exhibited equilibrium stoichiometries of 1:10 and 1:4 at neutral and low pH. The G4ACE-FA:5-FU:SF complex displayed stoichiometries of 1:11:10 at neutral pH and 1:3:3 a","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405964","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}
引用次数: 0
New Advances in Understanding Inhibition of Myeloperoxidase and Neutrophil Serine Proteases by Two Families of Staphylococcal Innate Immune Evasion Proteins 了解两个葡萄球菌先天性免疫规避蛋白家族抑制髓过氧化物酶和中性粒细胞丝氨酸蛋白酶的新进展
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-09 DOI: 10.1016/j.abb.2024.110177
{"title":"New Advances in Understanding Inhibition of Myeloperoxidase and Neutrophil Serine Proteases by Two Families of Staphylococcal Innate Immune Evasion Proteins","authors":"","doi":"10.1016/j.abb.2024.110177","DOIUrl":"10.1016/j.abb.2024.110177","url":null,"abstract":"<div><div>Neutrophils are the most abundant leukocytes in humans and play an important early role in the innate immune response against microorganisms. Neutrophil phagosomes contain high concentrations of antibacterial enzymes, including myeloperoxidase (MPO) and the neutrophil serine proteases (NSPs). These antibacterial enzymes can also be released extracellularly upon degranulation or as a component of neutrophil extracellular traps (NETs). Due to host/pathogen coevolution, <em>S. aureus</em> expresses a diverse arsenal of innate immune evasion proteins that target many aspects of the neutrophil antibacterial response. In the last decade, two new classes of staphylococcal innate immune evasion proteins that act as potent, selective inhibitors of MPO and NSPs, respectively, have been discovered. The Staphylococcal Peroxidase INhibitor (SPIN) is a small ∼8.3 kDa α-helical bundle protein that blocks MPO activity by interfering with substrate and product exchange with the MPO active site. The Extracellular Adherence Protein (EAP) family consists of three unique proteins comprised of one or more copies of an ∼11 kDa β-grasp domain capable of high-affinity, selective, non-covalent inhibition of NSPs. This brief review article summarizes recent advances in understanding the structural and functional properties of SPIN and EAP family members and outlines some potential avenues for future investigation of these enzyme inhibitors.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405965","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}
引用次数: 0
The LncRNA6524/miR-92a-2-5p/Dvl1/Wnt/β-catenin axis promotes renal fibrosis in the UUO mouse model LncRNA6524/miR-92a-2-5p/Dvl1/Wnt/β-catenin轴促进了UUO小鼠模型的肾脏纤维化。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-09 DOI: 10.1016/j.abb.2024.110175
{"title":"The LncRNA6524/miR-92a-2-5p/Dvl1/Wnt/β-catenin axis promotes renal fibrosis in the UUO mouse model","authors":"","doi":"10.1016/j.abb.2024.110175","DOIUrl":"10.1016/j.abb.2024.110175","url":null,"abstract":"<div><div>LncRNAs are reported to participate in multiple biological and pathological processes, including renal fibrosis due to obstructive nephropathy. However, the function and mechanisms of each lncRNA in this context differ. In this study, we created a fibrosis model in vitro using TGF-β1 treatment and in vivo through unilateral ureteral obstruction. We demonstrated that lncRNA6524 expression increased in both models, as confirmed by qPCR. Additionally, we discovered that lncRNA6524 mediates the TGF-β1-induced accumulation of extracellular matrix (ECM) proteins in BUMPT cells. We investigated the mechanism using dual luciferase reporter assays, immunofluorescence, and qPCR. Our results indicate that lncRNA6524 acts as a sponge for miR-92a-2-5p, promoting renal fibrosis by upregulating the Dvl1/Wnt/β-catenin signaling pathway. In summary, our findings demonstrate a linear regulatory relationship among lncRNA6524, miR-92a-2-5p, and the Dvl1/Wnt/β-catenin axis in renal epithelial cells during kidney obstruction. This highlights a new potential target for treating obstruction-related renal fibrosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399204","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}
引用次数: 0
Runx2 silencing sensitized human renal cell carcinoma cells to ABT-737 apoptosis Runx2沉默使人类肾细胞癌细胞对ABT-737凋亡敏感。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-05 DOI: 10.1016/j.abb.2024.110173
{"title":"Runx2 silencing sensitized human renal cell carcinoma cells to ABT-737 apoptosis","authors":"","doi":"10.1016/j.abb.2024.110173","DOIUrl":"10.1016/j.abb.2024.110173","url":null,"abstract":"<div><div>The prognostic value of Runt-related transcription factor 2 (Runx2) and its involvement in cell growth and motility have been reported in patients diagnosed with renal cell carcinoma (RCC). Since Runx2 may have the potential to be a target for the purpose of antitumor intervention, there is an urgent need to gain insight into its oncogenic properties. Using human 786-O, Caki-1 and ACHN RCC cells as models, the silencing of cellular Runx2 expression brought about a reduction in cyclin D1 and β-catenin expression, cell growth and migration without any significant cell death. Runx2-silenced cells turned into apoptosis vulnerable in the presence of ABT-737, a BH3 mimetic Bcl-2 inhibitor. Data from biochemical and molecular studies have revealed a positive correlation between Runx2 expression and Akt phosphorylation, Mcl-1 expression, and fibronectin expression. Results of genetic silencing studies have indicated the potential involvement of Mcl-1 and fibronectin in the decision of RCC cell ABT-737 resistance and sensitivity. The regulatory roles of the PI3K/Akt axis in the expression of Mcl-1 and fibronectin were suggested by means of the results taken from experiments involving pharmacological study of the PI3K/Akt. Since overexpression and prognostic roles of Runx2, activated Akt, Mcl-1, fibronectin, cyclin D1, and β-catenin have been revealed in RCC, it is important to explore the precise mechanisms underlying Runx2 oncogenic effects. Although the linking details between Runx2 and PI3K/Akt have yet to be identified, our findings suggest that Mcl-1 and fibronectin are downstream effectors of Runx2 via a regulatory axis of the PI3K/Akt and their promotion of cell growth, migration, and ABT-737 resistance in RCC cells.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379929","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}
引用次数: 0
The role of short-chain fatty acids in cancer prevention and cancer treatment 短链脂肪酸在癌症预防和治疗中的作用。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-04 DOI: 10.1016/j.abb.2024.110172
{"title":"The role of short-chain fatty acids in cancer prevention and cancer treatment","authors":"","doi":"10.1016/j.abb.2024.110172","DOIUrl":"10.1016/j.abb.2024.110172","url":null,"abstract":"<div><div>Short-chain fatty acids (SCFAs) are microbial metabolites in the gut that may play a role in cancer prevention and treatment. They affect the metabolism of both normal and cancer cells, regulating various cellular energetic processes. SCFAs also inhibit histone deacetylases, which are targets for cancer therapy. The three main SCFAs are acetate, propionate, and butyrate, which are transported into cells through specific transporters. SCFAs may enhance the efficacy of chemotherapeutic agents and modulate immune cell metabolism, potentially reprogramming the tumor microenvironment. Although SCFAs and SCFA-generating microbes enhance therapeutic efficacy of several forms of cancer therapy, published data also support the opposing viewpoint that SCFAs mitigate the efficacy of some cancer therapies. Therefore, the relationship between SCFAs and cancer is more complex, and this review discusses some of these aspects. Clearly, further research is needed to understand the role of SCFAs, their mechanisms, and applications in cancer prevention and treatment.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379930","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}
引用次数: 0
Harnessing high potential benzothiazole chalcones against dengue virus NS5 protein: A multi-faceted theoretical study through molecular docking, ADME, and DFT 利用高潜力苯并噻唑查尔酮对抗登革热病毒 NS5 蛋白:通过分子对接、ADME 和 DFT 进行的多方面理论研究。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-02 DOI: 10.1016/j.abb.2024.110171
{"title":"Harnessing high potential benzothiazole chalcones against dengue virus NS5 protein: A multi-faceted theoretical study through molecular docking, ADME, and DFT","authors":"","doi":"10.1016/j.abb.2024.110171","DOIUrl":"10.1016/j.abb.2024.110171","url":null,"abstract":"<div><div>Chalcones bearing tetralone, indanone and benzothiazole cores were synthesized successfully using a general Claisen-Schmidt condensation protocol. The prepared compounds were purified and structurally analyzed by <sup>1</sup>H, <sup>13</sup>C NMR, and FT-IR techniques. A multi-faceted theoretical approach, combining Density Functional Theory (DFT), molecular docking, and ADME predictions, was employed to evaluate their therapeutic potential. DFT calculations at the B3LYP/def2-TZVP level revealed key electronic properties, with TD3 compound demonstrating the highest chemical reactivity. Molecular Electrostatic Potential (MEP) and Reduced Density Gradient (RDG) analyses provided insights into the compounds' non-covalent interactions and charge distributions. Molecular docking studies against the NS5 protein (PDB: <span><span>6KR2</span><svg><path></path></svg></span>) showed superior binding affinities for all three compounds compared to the control ligand SAH, with TD3 exhibiting the lowest binding energy (−8.41 kcal/mol) and theoretical inhibition constant (689.31 nM). ADME predictions indicated favorable drug-like properties with concerns regarding aqueous solubility and potential P-glycoprotein interactions. Toxicity evaluations highlighted challenges, particularly in hepatotoxicity and carcinogenicity. The study identified TD3 as a promising lead compound for Dengue Virus NS5 inhibition, while also emphasizing the need for targeted modifications to address toxicity concerns. This research not only contributes to anti-dengue drug discovery efforts but also provides a robust methodological framework for the theoretical evaluation of similar small compounds in future investigations.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374990","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}
引用次数: 0
The LINC00319 binding to STAT3 promotes the cell proliferation, migration, invasion and EMT process in oral squamous cell carcinoma LINC00319 与 STAT3 结合可促进口腔鳞状细胞癌的细胞增殖、迁移、侵袭和 EMT 过程。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-02 DOI: 10.1016/j.abb.2024.110170
{"title":"The LINC00319 binding to STAT3 promotes the cell proliferation, migration, invasion and EMT process in oral squamous cell carcinoma","authors":"","doi":"10.1016/j.abb.2024.110170","DOIUrl":"10.1016/j.abb.2024.110170","url":null,"abstract":"<div><h3>Background</h3><div>Long non-coding RNA LINC00319 has been implicated in the progression of various cancers, including oral squamous cell carcinoma (OSCC). While our previous work has revealed some aspects of LINC00319's role in OSCC, including its upregulation and involvement in a competing endogenous RNA (ceRNA) mechanism, the full extent of its functions and regulatory mechanisms in OSCC progression remain to be fully elucidated.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the function of LINC00319 in OSCC and its potential interaction with the STAT3 signaling pathway, thus uncovering novel regulatory mechanisms and therapeutic targets.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis was performed using TCGA data to evaluate LINC00319 expression in OSCC tissues and its correlation with STAT3 signaling. The direct binding between LINC00319 and STAT3 was examined by RNA pull-down, FISH, and RIP assays. Functional experiments, including CCK-8, transwell migration and invasion assays, and western blot analysis of EMT markers and STAT3 pathway activation, were conducted to assess the effects of LINC00319 on OSCC cell behaviors and its interaction with the STAT3 signaling pathway. In vivo xenograft models were established to validate the role of LINC00319 in tumor growth and STAT3 activation.</div></div><div><h3>Results</h3><div>LINC00319 expression was significantly upregulated in OSCC tissues compared to normal tissues, and high LINC00319 expression correlated with STAT3 signaling activation. Mechanistically, LINC00319 directly bound to STAT3 protein and promoted its phosphorylation at Tyr705. LINC00319 overexpression enhanced, while its knockdown suppressed, the proliferation, migration, invasion, and EMT of OSCC cells. These oncogenic effects were mediated through STAT3 activation and could be reversed by the STAT3 inhibitor stattic. In vivo experiments further confirmed that LINC00319 silencing inhibited tumor growth and STAT3 phosphorylation.</div></div><div><h3>Conclusion</h3><div>This study uncovers that LINC00319 promotes OSCC tumorigenesis by directly binding to and activating STAT3 signaling. These findings provide new insights into the regulatory mechanisms of STAT3 by long non-coding RNAs and highlight the potential of LINC00319 as a biomarker and therapeutic target in OSCC.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374991","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}
引用次数: 0
Wnt3a-induced LRP6 phosphorylation enhances osteoblast differentiation to alleviate osteoporosis through activation of mTORC1/β-catenin signaling Wnt3a诱导的LRP6磷酸化可通过激活mTORC1/β-catenin信号增强成骨细胞分化,从而缓解骨质疏松症。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-10-01 DOI: 10.1016/j.abb.2024.110169
{"title":"Wnt3a-induced LRP6 phosphorylation enhances osteoblast differentiation to alleviate osteoporosis through activation of mTORC1/β-catenin signaling","authors":"","doi":"10.1016/j.abb.2024.110169","DOIUrl":"10.1016/j.abb.2024.110169","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoporosis (OP) is a common cause of morbidity and mortality in older individuals. The importance of Wnt3a in osteogenic activity and bone tissue homeostasis is well known. Here, we explored the possible molecular mechanism by which Wnt3a mediates the LRP6/mTORC1/β-catenin axis to regulate osteoblast differentiation in OP.</div></div><div><h3>Methods</h3><div>OP-related key genes were identified through a bioinformatics analysis. A ROS17/2.8 cell differentiation system for rat osteogenic progenitors and a rat model of senile OP were constructed for <em>in vitro</em> and <em>in vivo</em> mechanism verification.</div></div><div><h3>Results</h3><div>Bioinformatics analysis revealed that LRP6 was poorly expressed in OP and may play a key role in the occurrence of OP by affecting osteoblast differentiation. LRP6 knockdown inhibited osteoblast differentiation in an <em>in vitro</em> model. In addition, Wnt3a promoted osteoblast differentiation by inducing LRP6 phosphorylation. Moreover, LRP6 promoted mTORC1 expression, which indirectly promoted β-catenin expression, thus promoting osteoblast differentiation. Finally, an <em>in vivo</em> assay revealed that LRP6 inhibition improved OP.</div></div><div><h3>Conclusion</h3><div>Our study provides evidence that Wnt3a induces phosphorylation of LRP6 to activate the mTORC1/β-catenin axis, thus promoting osteoblast differentiation and ultimately improving OP in aged rats.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370831","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}
引用次数: 0
Heightened TPD52 linked to metabolic dysfunction and associated abnormalities in zebrafish TPD52 增高与斑马鱼代谢功能障碍及相关异常有关。
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2024-09-29 DOI: 10.1016/j.abb.2024.110166
{"title":"Heightened TPD52 linked to metabolic dysfunction and associated abnormalities in zebrafish","authors":"","doi":"10.1016/j.abb.2024.110166","DOIUrl":"10.1016/j.abb.2024.110166","url":null,"abstract":"<div><div>The tumor protein D52 (TPD52) gene encodes a proto-oncogene protein associated with various medical conditions, including breast and prostate cancers. It plays a role in multiple biological pathways such as cell growth, differentiation, and apoptosis. The function of TPD52 in lipid droplet biosynthesis has been investigated <em>in vitro</em>. However, its precise role in lipid metabolism in animal models is not fully understood. To investigate the functions of TPD52 in vivo, we performed a conditional TPD52 protein expression analysis using a Tet-off transgenic system to establish conditionally expressed Tpd52 transgenic zebrafish. The effect of Tpd52 on lipogenesis was assessed using various methods, including whole-mount Oil Red O staining, histological examination, and measurement of inflammatory markers and potential targets using real-time quantitative polymerase chain reaction and immunoblotting in Tpd52 fish. Zebrafish with increased Tpd52 levels exhibited notable weight gain and the enlargement of fat deposits, which were mainly attributed to an increase in the volume of adipocytes. Moreover, Tpd52 overexpression was correlated with the triggering of the adipocyte differentiation signaling pathway. During adipocytic differentiation in response to nutrient status, our observations revealed adipogenesis, nonalcoholic fatty liver disease, and metabolic cardiomyopathy (MCM) in Tpd52 transgenic zebrafish. To gain a deeper understanding of the contribution of these proteins to the regulation of cellular growth, we investigated the expression of their corresponding genes and proteins in zebrafish. In the present study, the activated protein kinase pathway was identified as the primary target of TPD52. Adult Tpd52 zebrafish showed increased lipid accumulation, resulting in the development of visceral obesity, nonalcoholic fatty liver disease, and MCM. These findings strongly suggest that TPD52 actively contributes to adipose tissue expansion and its subsequent effects. This investigation provides compelling evidence that Tpd52 facilitates adipocyte development and related metabolic comorbidities in zebrafish.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339966","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信