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Kinetic characterization of amino acid activation by aminoacyl-tRNA synthetases using radiolabelled γ-[32P]ATP. 使用放射性标记的 γ-[32P]ATP 分析氨基酰-tRNA 合成酶活化氨基酸的动力学特征。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-30 DOI: 10.1002/2211-5463.13903
Igor Živković, Morana Dulic, Petra Kozulic, Marko Mocibob, Ita Gruic-Sovulj
{"title":"Kinetic characterization of amino acid activation by aminoacyl-tRNA synthetases using radiolabelled γ-[<sup>32</sup>P]ATP.","authors":"Igor Živković, Morana Dulic, Petra Kozulic, Marko Mocibob, Ita Gruic-Sovulj","doi":"10.1002/2211-5463.13903","DOIUrl":"https://doi.org/10.1002/2211-5463.13903","url":null,"abstract":"<p><p>Aminoacyl-tRNA synthetases (AARSs) are fundamental enzymes that pair amino acids and tRNAs for protein synthesis. Aminoacylation occurs in two discrete steps. The amino acid is first activated by ATP, leading to an aminoacyl-adenylate intermediate and pyrophosphate (PP<sub>i</sub>) formation. In a subsequent step, the aminoacyl moiety is transferred to the tRNA. Kinetic assays were developed to follow each of these steps independently, as well as cumulative two-step aminoacylation. The main advantage of following the activation step over two-step aminoacylation is that most AARSs can activate amino acids in the absence of the tRNA, the production of which is laborious. Hence, the activation step is often tested first in the kinetic analysis, including large screens exploring AARS-targeting inhibitors. Since the 1960s, the activation reaction has been routinely followed by the standard ATP/[<sup>32</sup>P]PP<sub>i</sub> exchange assay, which relies on the equilibrium exchange of radiolabel between PP<sub>i</sub> and ATP using [<sup>32</sup>P]PP<sub>i</sub> as a labelled compound. However, this method became much less convenient when [<sup>32</sup>P]PP<sub>i</sub> was discontinued in 2022. As a solution, we developed a modified assay that uses easily attainable γ-[<sup>32</sup>P]ATP as a labelled compound in the equilibrium-based assay. Using this assay, herein named the [<sup>32</sup>P]ATP/PP<sub>i</sub> assay, we followed the activation step of several AARSs. The obtained data are in good agreement with the previously published kinetic constants obtained with the standard ATP/[<sup>32</sup>P]PP<sub>i</sub> exchange assay.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biogenesis of mitochondrial β-barrel membrane proteins 线粒体β管膜蛋白的生物生成。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-29 DOI: 10.1002/2211-5463.13905
Iniyan Ganesan, Jon V. Busto, Nikolaus Pfanner, Nils Wiedemann
{"title":"Biogenesis of mitochondrial β-barrel membrane proteins","authors":"Iniyan Ganesan,&nbsp;Jon V. Busto,&nbsp;Nikolaus Pfanner,&nbsp;Nils Wiedemann","doi":"10.1002/2211-5463.13905","DOIUrl":"10.1002/2211-5463.13905","url":null,"abstract":"<p>β-barrel membrane proteins in the mitochondrial outer membrane are crucial for mediating the metabolite exchange between the cytosol and the mitochondrial intermembrane space. In addition, the β-barrel membrane protein subunit Tom40 of the translocase of the outer membrane (TOM) is essential for the import of the vast majority of mitochondrial proteins encoded in the nucleus. The sorting and assembly machinery (SAM) in the outer membrane is required for the membrane insertion of mitochondrial β-barrel proteins. The core subunit Sam50, which has been conserved from bacteria to humans, is itself a β-barrel protein. The β-strands of β-barrel precursor proteins are assembled at the Sam50 lateral gate forming a Sam50-preprotein hybrid barrel. The assembled precursor β-barrel is finally released into the outer mitochondrial membrane by displacement of the nascent β-barrel, termed the β-barrel switching mechanism. SAM forms supercomplexes with TOM and forms a mitochondrial outer-to-inner membrane contact site with the mitochondrial contact site and cristae organizing system (MICOS) of the inner membrane. SAM shares subunits with the ER-mitochondria encounter structure (ERMES), which forms a membrane contact site between the mitochondrial outer membrane and the endoplasmic reticulum. Therefore, β-barrel membrane protein biogenesis is closely connected to general mitochondrial protein and lipid biogenesis and plays a central role in mitochondrial maintenance.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 10","pages":"1595-1609"},"PeriodicalIF":2.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response 肺腺癌中的 SMARCA4 突变和表达:预后意义及对免疫疗法反应的影响。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-25 DOI: 10.1002/2211-5463.13899
Yuming Zhang, Dantong Sun, Weizhong Han, Zhen Yang, Yongzhi Lu, Xuchen Zhang, Yongjie Wang, Chuantao Zhang, Ning Liu, Helei Hou
{"title":"SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response","authors":"Yuming Zhang,&nbsp;Dantong Sun,&nbsp;Weizhong Han,&nbsp;Zhen Yang,&nbsp;Yongzhi Lu,&nbsp;Xuchen Zhang,&nbsp;Yongjie Wang,&nbsp;Chuantao Zhang,&nbsp;Ning Liu,&nbsp;Helei Hou","doi":"10.1002/2211-5463.13899","DOIUrl":"10.1002/2211-5463.13899","url":null,"abstract":"<p>The switch/sucrose non-fermenting (SWI/SNF) complex family includes important chromatin-remodeling factors that are frequently mutated in lung adenocarcinoma (LUAD). However, the role of one family member, <i>SMARCA4</i>, in LUAD prognosis and immunotherapy sensitivity remains unclear. In the present study, 6745 LUAD samples from the cBioPortal database were used to analyze the relationships between <i>SMARCA4</i> mutations and patient prognoses and clinical characteristics. Additionally, we examined the correlation between <i>SMARCA4</i> mutations and prognosis in patients treated with immunotherapy using two immune-related datasets. <i>SMARCA4</i> mutations and low expression were associated with shorter survival, and mutations were associated with a high tumor mutational burden and high microsatellite instability. <i>SMARCA4</i> mutations were accompanied by <i>KRAS</i>, <i>KEAP1</i>, <i>TP53</i> and <i>STK11</i> mutations. No significant difference was observed in the immunotherapy response between patients with and without <i>SMARCA4</i> mutations. When <i>KRAS</i> or <i>STK11</i> mutations were present, immunotherapy effectiveness was poorer; however, when both <i>SMARCA4</i> and <i>TP53</i> mutations were present, immunotherapy was more effective. Furthermore, low <i>SMARCA4</i> expression predicted a higher immunophenoscore, and <i>SMARCA4</i> expression was correlated with certain immune microenvironment features. Taken together, our results suggest that <i>SMARCA4</i> mutations and low expression might be associated with poor LUAD prognosis. Additionally, immunotherapy efficacy in patients with <i>SMARCA4</i> mutations depended on the co-mutant genes. Thus, <i>SMARCA4</i> could be an important factor to be considered for LUAD diagnosis and treatment.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 12","pages":"2086-2103"},"PeriodicalIF":2.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis 14K 催乳素衍生的 14-mer抗血管生成肽靶向缓激肽-/一氧化氮-GMP 依赖性血管生成。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-23 DOI: 10.1002/2211-5463.13895
Jaeok Lee, Pavitra Kumar, Suganya Natarajan, So Hyeon Park, Syamantak Majumder, Lakshmikirupa Sundaresan, Kambadur Muralidhar, Jong-Soon Choi, Hwa Jeong Lee, Suvro Chatterjee
{"title":"14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis","authors":"Jaeok Lee,&nbsp;Pavitra Kumar,&nbsp;Suganya Natarajan,&nbsp;So Hyeon Park,&nbsp;Syamantak Majumder,&nbsp;Lakshmikirupa Sundaresan,&nbsp;Kambadur Muralidhar,&nbsp;Jong-Soon Choi,&nbsp;Hwa Jeong Lee,&nbsp;Suvro Chatterjee","doi":"10.1002/2211-5463.13895","DOIUrl":"10.1002/2211-5463.13895","url":null,"abstract":"<p>Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14 kDa buffalo prolactin and characterized its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology, BK)-stimulated endothelial nitric oxide (eNO) production, cell migration, and proliferation in endothelial cells and vessel development in the chick embryo. Although this peptide inhibited both VEGF- and BK-dependent angiogenic processes, its action was more pronounced in the latter. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was also identified. A combination of a low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in an <i>in vivo</i> model of human colon cancer. Taken together, our results suggest that 14-MAP, a BK- and eNOS-dependent antiangiogenic peptide, might be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients. However, further studies will be required to further characterize its mode of action and therapeutic potential.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 12","pages":"2072-2085"},"PeriodicalIF":2.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13895","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
An outlook on structural biology after AlphaFold: tools, limits and perspectives. AlphaFold 之后的结构生物学展望:工具、局限和前景。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-23 DOI: 10.1002/2211-5463.13902
Serena Rosignoli, Maddalena Pacelli, Francesca Manganiello, Alessandro Paiardini
{"title":"An outlook on structural biology after AlphaFold: tools, limits and perspectives.","authors":"Serena Rosignoli, Maddalena Pacelli, Francesca Manganiello, Alessandro Paiardini","doi":"10.1002/2211-5463.13902","DOIUrl":"https://doi.org/10.1002/2211-5463.13902","url":null,"abstract":"<p><p>AlphaFold and similar groundbreaking, AI-based tools, have revolutionized the field of structural bioinformatics, with their remarkable accuracy in ab-initio protein structure prediction. This success has catalyzed the development of new software and pipelines aimed at incorporating AlphaFold's predictions, often focusing on addressing the algorithm's remaining challenges. Here, we present the current landscape of structural bioinformatics shaped by AlphaFold, and discuss how the field is dynamically responding to this revolution, with new software, methods, and pipelines. While the excitement around AI-based tools led to their widespread application, it is essential to acknowledge that their practical success hinges on their integration into established protocols within structural bioinformatics, often neglected in the context of AI-driven advancements. Indeed, user-driven intervention is still as pivotal in the structure prediction process as in complementing state-of-the-art algorithms with functional and biological knowledge.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
YAP-TEAD inhibition is associated with upregulation of an androgen receptor mediated transcription program providing therapeutic escape YAP-TEAD抑制与雄激素受体介导的转录程序上调有关,从而提供了治疗逃逸。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-19 DOI: 10.1002/2211-5463.13901
Roberto Alva-Ruiz, Ryan D. Watkins, Jennifer L. Tomlinson, Jennifer A. Yonkus, Amro M. Abdelrahman, Caitlin B. Conboy, Erik Jessen, Nathan W. Werneburg, Hendrien Kuipers, Jack W. Sample, Gregory J. Gores, Sumera I. Ilyas, Mark J. Truty, Rory L. Smoot
{"title":"YAP-TEAD inhibition is associated with upregulation of an androgen receptor mediated transcription program providing therapeutic escape","authors":"Roberto Alva-Ruiz,&nbsp;Ryan D. Watkins,&nbsp;Jennifer L. Tomlinson,&nbsp;Jennifer A. Yonkus,&nbsp;Amro M. Abdelrahman,&nbsp;Caitlin B. Conboy,&nbsp;Erik Jessen,&nbsp;Nathan W. Werneburg,&nbsp;Hendrien Kuipers,&nbsp;Jack W. Sample,&nbsp;Gregory J. Gores,&nbsp;Sumera I. Ilyas,&nbsp;Mark J. Truty,&nbsp;Rory L. Smoot","doi":"10.1002/2211-5463.13901","DOIUrl":"10.1002/2211-5463.13901","url":null,"abstract":"<p>Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer and is an increasing cause of cancer-related death worldwide. Despite its increasing incidence globally and alarming mortality, treatment options for CCA have largely remained unchanged, stressing the importance of developing new effective therapies. YAP activation is common in CCA, and its major transcriptional signaling partners are the TEAD proteins. CA3 is a small-molecule YAP-TEAD disrupter discovered utilizing a TEAD reporter assay. Utilizing CCA, gastric cancer cell lines, and patient-derived xenograft models (PDX), we demonstrate that CA3 is effective in inducing cell death and delaying tumor growth in both <i>FGFR2</i> fusion and wild-type models. CA3 was associated with on-target decreases in YAP-TEAD target gene expression, TEAD reporter activity, and overall TEAD levels. Hippo pathway signaling was not altered as there was no change in YAP phosphorylation status in the cells exposed to CA3. RNA sequencing of gastric cancer and CCA models demonstrated upregulation of an androgen receptor–mediated transcriptional program following exposure to CA3 in five unique models tested. Consistent with this upstream regulator analysis, CA3 exposure in CCA cells was associated with increased AR protein levels, and combinatorial therapy with CA3 and androgen receptor blockade was associated with increased cancer cell death. CA3 behaves functionally as a YAP-TEAD disrupter in the models tested and demonstrated therapeutic efficacy. Exposure to CA3 was associated with compensatory androgen receptor signaling and dual inhibition improved the therapeutic effect.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 11","pages":"1873-1887"},"PeriodicalIF":2.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Carbohydrate response element-binding protein (ChREBP) mediates decreased SNAP25 expression in islets from diabetic Goto-Kakizaki (GK) rats 碳水化合物反应元件结合蛋白(ChREBP)介导糖尿病后藤柿崎(GK)大鼠胰岛中 SNAP25 表达的降低。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-19 DOI: 10.1002/2211-5463.13900
Anyi Hu, Hongyan Lan, Zilai Yao, Xiangchen Kong
{"title":"Carbohydrate response element-binding protein (ChREBP) mediates decreased SNAP25 expression in islets from diabetic Goto-Kakizaki (GK) rats","authors":"Anyi Hu,&nbsp;Hongyan Lan,&nbsp;Zilai Yao,&nbsp;Xiangchen Kong","doi":"10.1002/2211-5463.13900","DOIUrl":"10.1002/2211-5463.13900","url":null,"abstract":"<p>SNAP25 plays an essential role in the glucose-stimulated insulin secretion (GSIS) of pancreatic β-cells. Carbohydrate response element-binding protein (ChREBP) is an important transcription factor in β-cells and, in this study, we aimed to explore whether ChREBP regulates SNAP25 expression in β-cells. We show that diabetic Goto-Kakizaki (GK) rats exhibited impaired insulin secretion and hyperglycemia, along with decreased SNAP25 expression and ChREBP phosphorylation in islets. SNAP25 knockdown decreased GSIS in β-cells, while SNAP25 overexpression increased GSIS in β-cells. Activation or overexpression of ChREBP led to reduced SNAP25 expression and subsequent suppression of GSIS. Conversely, ChREBP knockdown mitigated the reduction in SNAP25 expression caused by high glucose. Mechanistically, the activation of ChREBP by high glucose increased its occupancy and decreased the level of H3K4me3 at the <i>Snap25</i> promoter. Our findings reveal the novel regulatory mechanisms of SNAP25 expression in β-cells and suggest that SNAP25 may be involved in the regulation of β-cell secretory function controlled by ChREBP.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 11","pages":"1864-1872"},"PeriodicalIF":2.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Solvation free energy in governing equations for DNA hybridization, protein–ligand binding, and protein folding DNA 杂交、蛋白质-配体结合和蛋白质折叠的调控方程中的溶解自由能
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-17 DOI: 10.1002/2211-5463.13897
Caroline Harmon, Austin Bui, Jasmin M. Espejo, Marc Gancayco, Jennifer M. Le, Juan Rangel, Daryl K. Eggers
{"title":"Solvation free energy in governing equations for DNA hybridization, protein–ligand binding, and protein folding","authors":"Caroline Harmon,&nbsp;Austin Bui,&nbsp;Jasmin M. Espejo,&nbsp;Marc Gancayco,&nbsp;Jennifer M. Le,&nbsp;Juan Rangel,&nbsp;Daryl K. Eggers","doi":"10.1002/2211-5463.13897","DOIUrl":"10.1002/2211-5463.13897","url":null,"abstract":"<p>This work examines the thermodynamics of model biomolecular interactions using a governing equation that accounts for the participation of bulk water in the equilibria. In the first example, the binding affinities of two DNA duplexes, one of nine and one of 10 base pairs in length, are measured and characterized by isothermal titration calorimetry (ITC) as a function of concentration. The results indicate that the change in solvation free energy that accompanies duplex formation (Δ<i>G</i><sup>S</sup>) is large and unfavorable. The duplex with the larger number of G:C pairings yields the largest change in solvation free energy, Δ<i>G</i><sup>S</sup> = +460 kcal·mol<sup>−1</sup>per base pair at 25 °C. A van't Hoff analysis of the data is complicated by the varying degree of intramolecular base stacking within each DNA strand as a function of temperature. A modeling study reveals how the solvation free energy alters the output of a typical ITC experiment and leads to a good, though misleading, fit to the classical equilibrium equation. The same thermodynamic framework is applied to a model protein–ligand interaction, the binding of ribonuclease A with the nucleotide inhibitor 3′-UMP, and to a conformational equilibrium, the change in tertiary structure of α-lactalbumin in molar guanidinium chloride solutions. The ribonuclease study yields a value of Δ<i>G</i><sup>S</sup> = +160 kcal·mol<sup>−1</sup>, whereas the folding equilibrium yields Δ<i>G</i><sup>S</sup> ≈ 0, an apparent characteristic of hydrophobic interactions. These examples provide insight on the role of solvation energy in binding equilibria and suggest a pivot in the fundamental application of thermodynamics to solution chemistry.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 11","pages":"1837-1850"},"PeriodicalIF":2.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Transcriptional changes impact hepatic proteome in autophagy-impaired liver 转录变化影响自噬受损肝脏的肝蛋白质组
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-16 DOI: 10.1002/2211-5463.13898
Kamal Baral, Spandan Joshi, Adriana Lopez, Gavisha Mugon, Aroma Chanda, Arya A. Chandrasheker, Cameron Hinton, Kapil Thapa, Arissa Mercer, Leah Spade, Gang Liu, Bhupal Prasad Bhetwal, Jia Fang, Bilon Khambu
{"title":"Transcriptional changes impact hepatic proteome in autophagy-impaired liver","authors":"Kamal Baral,&nbsp;Spandan Joshi,&nbsp;Adriana Lopez,&nbsp;Gavisha Mugon,&nbsp;Aroma Chanda,&nbsp;Arya A. Chandrasheker,&nbsp;Cameron Hinton,&nbsp;Kapil Thapa,&nbsp;Arissa Mercer,&nbsp;Leah Spade,&nbsp;Gang Liu,&nbsp;Bhupal Prasad Bhetwal,&nbsp;Jia Fang,&nbsp;Bilon Khambu","doi":"10.1002/2211-5463.13898","DOIUrl":"10.1002/2211-5463.13898","url":null,"abstract":"<p>Hepatic proteomes are intricately controlled through biosynthesis, extracellular secretion, and intrahepatic degradation. Autophagy governs lysosome-mediated intrahepatic degradation and the hepatic proteome. When autophagy is impaired, it leads to the accumulation of intrahepatic proteins, causing proteinopathy. This study investigates whether autophagy can modulate the hepatic proteome non-degradatively. Utilizing conditional, inducible, and hepatotoxin models of hepatic autophagy impairment, we assessed the overall hepatic proteome expression using Coomassie brilliant blue (CBB) staining and liquid chromatography–tandem mass spectrometry (LC/MS). We pinpointed and confirmed four specific hepatic proteins—Cps1, Ahcy, Ca3, and Gstm1—that were selectively modified in autophagy-deficient livers. Expression of Cps1, Ahcy, and Ca3 were significantly reduced, while Gstm1 expression increased in livers with autophagy impairment. Interestingly, these changes in hepatic protein levels were not due to defective autophagic degradation but were associated with alterations in mRNA transcript levels. Moreover, as a result of autophagic dysfunction, sustained activation of the nuclear erythroid-derived 2-like 2 (Nrf2) transcription factor, transcriptionally regulated the mRNA levels of these proteins. Our findings indicate that autophagy can influence hepatic proteins not solely via traditional degradative routes but also through non-degradative transcriptional processes by modulating Nrf2.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 11","pages":"1851-1863"},"PeriodicalIF":2.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13898","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Metagenomic analysis of the gut microbiota of hooded cranes (Grus monacha) on the Izumi plain in Japan 日本泉平原冠鹤肠道微生物群的元基因组分析
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2024-09-14 DOI: 10.1002/2211-5463.13881
Kosuke Takada, So Nakagawa, Kirill Kryukov, Makoto Ozawa, Tokiko Watanabe
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