Biochimica et biophysica acta. General subjects最新文献

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Identification and classification of proteins by FTIR microspectroscopy. A proof of concept 利用傅立叶变换红外微光谱对蛋白质进行鉴定和分类。概念验证。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-08-06 DOI: 10.1016/j.bbagen.2024.130688
Christophe Sandt
{"title":"Identification and classification of proteins by FTIR microspectroscopy. A proof of concept","authors":"Christophe Sandt","doi":"10.1016/j.bbagen.2024.130688","DOIUrl":"10.1016/j.bbagen.2024.130688","url":null,"abstract":"<div><p>FTIR spectroscopy is well known for its molecule fingerprinting capability but is also able to differentiate classes in complex biological systems. This includes strain typing and species level identification of bacterial, yeast or fungal cells, as well as distinguishing between cell layers in eukaryotic tissues. However, its use for the identification of macromolecules such as proteins remains underexplored and rarely used in practice. Here we demonstrate the efficacy of FTIR microspectroscopy coupled with machine learning methods for rapid and accurate identification of proteins in their dry state within minutes, from very small quantities of material, if they are obtained in a pure aqueous solution. FTIR microspectroscopy can provide additional information beside identification: it can detect small differences among different purification batches potentially originating from post-translational modifications or distinct folding states. Moreover, it distinguishes glycoproteins and evaluate glycosylation while detecting contaminants. This methodology presents itself as a valuable quality control tool in protein purification processes or any process requiring the utilization of precisely identified, pure proteins.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905743","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
Key charged residues influence the amyloidogenic propensity of the helix-1 region of serum amyloid A 关键带电残基影响血清淀粉样蛋白 A 的螺旋-1 区域的淀粉样化倾向。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-08-06 DOI: 10.1016/j.bbagen.2024.130690
Marvin Bilog , Jayson Vedad , Charisse Capadona , Adam A. Profit , Ruel Z.B. Desamero
{"title":"Key charged residues influence the amyloidogenic propensity of the helix-1 region of serum amyloid A","authors":"Marvin Bilog ,&nbsp;Jayson Vedad ,&nbsp;Charisse Capadona ,&nbsp;Adam A. Profit ,&nbsp;Ruel Z.B. Desamero","doi":"10.1016/j.bbagen.2024.130690","DOIUrl":"10.1016/j.bbagen.2024.130690","url":null,"abstract":"<div><p>Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA. Moreover, computational studies implicated a significant role for Arg-1 and the residue-specific interactions formed during the fibrillization process. With a focus on the N-terminal region of helix-1, SAA<sub>1–13</sub>, mutational analysis was employed to interrogate the roles of the amino acid residues, Arg-1, Ser-5, Glu-9, and Asp-12. The truncated SAA<sub>1–13</sub> fragment was systematically modified by substituting the key residues with alanine or uncharged but structurally similar amino acids. We monitored the changes in the amyloidogenic propensities, associated conformational markers, and morphology of the amyloids resulting from the mutation of SAA<sub>1–13</sub>. Mutating out Arg-1 resulted in much reduced aggregation propensity and a lack of detectable β-structures alluding to the importance of salt-bridge interactions involving Arg-1. Our data revealed that by systematically mutating the key amino acid residues, we can modulate the amyloidogenic propensity and alter the time-dependent conformational variation of the peptide. When the behaviors of each mutant peptide were analyzed, they provided evidence consistent with the aggregation pathway predicted by MD simulation studies. Here, we detail the important temporal molecular interactions formed by Arg-1 with Ser-5, Glu-9, and Asp-12 and discuss its mechanistic implications on the self-assembly of the helix-1 region of SAA.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905744","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
Emphasizing laccase based amperometric biosensing as an eventual panpharmacon for rapid and effective detection of phenolic compounds 强调基于漆酶的安培生物传感技术是快速有效检测酚类化合物的最终泛药典。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-08-06 DOI: 10.1016/j.bbagen.2024.130691
Himani Guliya , Meena Yadav , Bhawna Nohwal , Suman Lata , Reeti Chaudhary
{"title":"Emphasizing laccase based amperometric biosensing as an eventual panpharmacon for rapid and effective detection of phenolic compounds","authors":"Himani Guliya ,&nbsp;Meena Yadav ,&nbsp;Bhawna Nohwal ,&nbsp;Suman Lata ,&nbsp;Reeti Chaudhary","doi":"10.1016/j.bbagen.2024.130691","DOIUrl":"10.1016/j.bbagen.2024.130691","url":null,"abstract":"<div><p>Phenols and phenolic compounds are major plant metabolites used in industries to produce pesticides, dyes, medicines, and plastics. These compounds enter water bodies, soil, and living organisms via such industrial routes. Some polyphenolic compounds like phenolic acids, flavonoids have antioxidant and organoleptic qualities, as well as preventive effects against neurodegenerative illnesses, cardiovascular disease, diabetes, and cancer. However, many of the polyphenolic compounds, such as Bisphenol A, phthalates, and dioxins also cause major environmental pollution and endocrine disruption, once the dose level becomes objectionable. The development of reliable and rapid methods for studying their dose dependency, high-impact detrimental effects, and continuous monitoring of phenol levels in humans and environmental samples is a crucial necessity of the day. Enzymatic biosensors employing phenol oxidases like tyrosinase, peroxidase and laccase, utilizing electrochemical amperometric methods are innovative methods for phenol quantification. Enzymatic biosensing, being highly sensitive and efficacious technique, is illuminated in this review article as a progressive approach for phenol quantification with special emphasis on laccase amperometric biosensors. Even more, the review article discussion is extended up to nanozymes, composites of metal organic frameworks (MOFs), and molecularly imprinted polymers (MIPs) as some emerging species for electro-chemical sensing of phenols. Applications of phenol quantification and green biosensing are also specified. A concrete summary of the innovative polyphenol detection approaches with futuristic scope indicates a triumph over some existing constraints of the phenomenological approaches providing an informative aisle to the modern researchers towards the bulk readability.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905742","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
Exploring domain architectures of human glycosyltransferases: Highlighting the functional diversity of non-catalytic add-on domains 探索人类糖基转移酶的结构域:突显非催化附加结构域的功能多样性
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-08-02 DOI: 10.1016/j.bbagen.2024.130687
Hirokazu Yagi , Katsuki Takagi , Koichi Kato
{"title":"Exploring domain architectures of human glycosyltransferases: Highlighting the functional diversity of non-catalytic add-on domains","authors":"Hirokazu Yagi ,&nbsp;Katsuki Takagi ,&nbsp;Koichi Kato","doi":"10.1016/j.bbagen.2024.130687","DOIUrl":"10.1016/j.bbagen.2024.130687","url":null,"abstract":"<div><p>Human glycosyltransferases (GTs) play crucial roles in glycan biosynthesis, exhibiting diverse domain architectures. This study explores the functional diversity of “add-on” domains within human GTs, using data from the AlphaFold Protein Structure Database. Among 215 annotated human GTs, 74 contain one or more add-on domains in addition to their catalytic domain. These domains include lectin folds, fibronectin type III, and thioredoxin-like domains and contribute to substrate specificity, oligomerization, and consequent enzymatic activity. Notably, certain GTs possess dual enzymatic functions due to catalytic add-on domains. The analysis highlights the importance of add-on domains in enzyme functionality and disease implications, such as congenital disorders of glycosylation. This comprehensive overview enhances our understanding of GT domain organization, providing insights into glycosylation mechanisms and potential therapeutic targets.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888380","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
Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy 靶向 SMYD2 可通过 c-Myc/NCOA4 轴介导的噬铁蛋白作用促进铁蛋白沉积并影响胰腺癌的进展。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-07-31 DOI: 10.1016/j.bbagen.2024.130683
Juan Tan , Shan Liao , Bowen Yuan , Xinrong Liu , Wentao Yu , Han Zhan , Yan Jiang , Yang Liu
{"title":"Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy","authors":"Juan Tan ,&nbsp;Shan Liao ,&nbsp;Bowen Yuan ,&nbsp;Xinrong Liu ,&nbsp;Wentao Yu ,&nbsp;Han Zhan ,&nbsp;Yan Jiang ,&nbsp;Yang Liu","doi":"10.1016/j.bbagen.2024.130683","DOIUrl":"10.1016/j.bbagen.2024.130683","url":null,"abstract":"<div><h3>Background</h3><p>Pancreatic cancer (PC) is characterized by a poor prognosis and limited treatment options. Ferroptosis plays an important role in cancer, SET and MYND domain-containing protein 2 (SMYD2) is widely expressed in various cancers. However, the role of SMYD2 in regulating ferroptosis in PC remains unexplored. This study aimed to investigate the role of SMYD2 in mediating ferroptosis and its mechanistic implications in PC progression.</p></div><div><h3>Methods</h3><p>The levels of SMYD2, c-Myc, and NCOA4 were assessed in PC tissues, and peritumoral tissues. SMYD2 expression was further analyzed in human PC cell lines. In BxPC3 cells, the expression of c-Myc, NCOA4, autophagy-related proteins, and mitochondrial morphology, was evaluated following transfection with si-SMYD2 and treatment with autophagy inhibitors and ferroptosis inhibitors. Ferroptosis levels were quantified using flow cytometry and ELISA assays. RNA immunoprecipitation was conducted to elucidate the interaction between c-Myc and NCOA4 mRNA. A xenograft mouse model was constructed to validate the impact of SMYD2 knockdown on PC growth.</p></div><div><h3>Results</h3><p>SMYD2 and c-Myc were found to be highly expressed in PC tissues, while NCOA4 showed reduced expression. Among the PC cell lines studied, BxPC3 cells exhibited the highest SMYD2 expression. SMYD2 knockdown led to decreased c-Myc levels, increased NCOA4 expression, reduced autophagy-related protein expression, mitochondrial shrinkage, and heightened ferroptosis levels. Additionally, an interaction between c-Myc and NCOA4 was identified. <em>In vivo</em>, SMYD2 knockdown inhibited tumor growth.</p></div><div><h3>Conclusions</h3><p>Targeting SMYD2 inhibits PC progression by promoting ferritinophagy-dependent ferroptosis through the c-Myc/NCOA4 axis. These findings provide insights into potential diagnostic and therapeutic strategies for PC.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874060","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 angiotensin II/type 1 angiotensin II receptor pathway is implicated in the dysfunction of albumin endocytosis in renal proximal tubule epithelial cells induced by high glucose levels 血管紧张素 II/1型血管紧张素 II 受体途径与高血糖诱导的肾近曲小管上皮细胞白蛋白内吞功能障碍有关。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-07-29 DOI: 10.1016/j.bbagen.2024.130684
Liz G. Afonso , Rodrigo P. Silva-Aguiar , Douglas E. Teixeira , Sarah A.S. Alves , Alvin H. Schmaier , Ana Acacia S. Pinheiro , Diogo B. Peruchetti , Celso Caruso-Neves
{"title":"The angiotensin II/type 1 angiotensin II receptor pathway is implicated in the dysfunction of albumin endocytosis in renal proximal tubule epithelial cells induced by high glucose levels","authors":"Liz G. Afonso ,&nbsp;Rodrigo P. Silva-Aguiar ,&nbsp;Douglas E. Teixeira ,&nbsp;Sarah A.S. Alves ,&nbsp;Alvin H. Schmaier ,&nbsp;Ana Acacia S. Pinheiro ,&nbsp;Diogo B. Peruchetti ,&nbsp;Celso Caruso-Neves","doi":"10.1016/j.bbagen.2024.130684","DOIUrl":"10.1016/j.bbagen.2024.130684","url":null,"abstract":"<div><p>It is well-established that dysfunction of megalin-mediated albumin endocytosis by proximal tubule epithelial cells (PTECs) and the activation of the Renin-Angiotensin System (RAS) play significant roles in the development of Diabetic Kidney Disease (DKD). However, the precise correlation between these factors still requires further investigation. In this study, we aimed to elucidate the potential role of angiotensin II (Ang II), a known effector of RAS, as the mediator of albumin endocytosis dysfunction induced by high glucose (HG) in PTECs. To achieve this, we utilized LLC-PK1 and HK-2 cells, which are well-established in vitro models of PTECs. Using albumin-FITC or DQ-albumin as tracers, we observed that incubation of LLC-PK1 and HK-2 cells with HG (25 mM for 48 h) significantly reduced canonical receptor-mediated albumin endocytosis, primarily due to the decrease in megalin expression. HG increased the concentration of Ang II in the LLC-PK1 cell supernatant, a phenomenon associated with an increase in angiotensin-converting enzyme (ACE) expression and a decrease in prolyl carboxypeptidase (PRCP) expression. ACE type 2 (ACE2) expression remained unchanged. To investigate the potential impact of Ang II on HG effects, the cells were co-incubated with angiotensin receptor inhibitors. Only co-incubation with 10<sup>−7</sup> M losartan (an antagonist for type 1 angiotensin receptor, AT<sub>1</sub>R) attenuated the inhibitory effect of HG on albumin endocytosis, as well as megalin expression. Our findings contribute to understanding the genesis of tubular albuminuria observed in the early stages of DKD, which involves the activation of the Ang II/AT<sub>1</sub>R axis by HG.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858863","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
CRISPR/Cas9 opens new horizon of crop improvement under stress condition CRISPR/Cas9 为逆境条件下的作物改良开辟了新天地
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-07-28 DOI: 10.1016/j.bbagen.2024.130685
Sanjib Patra , Debdatta Chatterjee , Shrabani Basak , Susmi Sen , Arunava Mandal
{"title":"CRISPR/Cas9 opens new horizon of crop improvement under stress condition","authors":"Sanjib Patra ,&nbsp;Debdatta Chatterjee ,&nbsp;Shrabani Basak ,&nbsp;Susmi Sen ,&nbsp;Arunava Mandal","doi":"10.1016/j.bbagen.2024.130685","DOIUrl":"10.1016/j.bbagen.2024.130685","url":null,"abstract":"<div><p>Plants are exposed to a myriad of stresses, stemming from abiotic and biotic sources, significantly threatening agricultural productivity. The low crop yield, coupled with the global burden of population has resulted in the scarcity of quality food, exacerbating socio-economic issues like poverty, hunger, and malnutrition. Conventional breeding methods for the generation of stress-tolerant plants are time-consuming, limit genetic diversity, and are not sustainable for the consistent production of high-yielding crops. In recent years, the use of high-throughput, genome editing (GE) technique has revolutionized the crop-improvement paradigm, ushering greater prospects for agricultural progress. Among these tools, the Clustered regularly interspaced short palindromic repeat (CRISPR), and its associated nuclease protein Cas9, have appeared as a ground-breaking technology, allowing precise knockout (KO), upregulation, and downregulation of target gene expression. Apart from its high efficacy and speed, this programmable nuclease offers exceptional specificity with minimal off-target effects. Here in, we aim to review the latest findings on the application of the CRISPR/Cas9 genome editing tool for generating resilience in plants against environmental stresses.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840443","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
B cell epitope mapping: The journey to better vaccines and therapeutic antibodies B 细胞表位图谱:通往更好的疫苗和治疗性抗体之路
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-07-28 DOI: 10.1016/j.bbagen.2024.130674
Asha Joanne De Leon , M. Christian Tjiam , Yu Yu
{"title":"B cell epitope mapping: The journey to better vaccines and therapeutic antibodies","authors":"Asha Joanne De Leon ,&nbsp;M. Christian Tjiam ,&nbsp;Yu Yu","doi":"10.1016/j.bbagen.2024.130674","DOIUrl":"10.1016/j.bbagen.2024.130674","url":null,"abstract":"<div><p>B-cell epitope mapping is an approach that can identify and characterise specific antigen binding sites of B-cell receptors and secreted antibodies. The ability to determine the antigenic clusters of amino acids bound by B-cell clones provides unprecedented detail that will aid in developing novel and effective vaccine targets and therapeutic antibodies for various diseases. Here, we discuss conventional approaches and emerging techniques that are used to map B-cell epitopes.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845549","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 combined inhibition of SLC1A3 and glutaminase in osimertinib-resistant EGFR mutant cells 在奥西美替尼耐药的表皮生长因子受体突变细胞中联合抑制 SLC1A3 和谷氨酰胺酶。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-07-24 DOI: 10.1016/j.bbagen.2024.130675
Nobuaki Ochi , Noriko Miyake , Masami Takeyama , Hiromichi Yamane , Takuya Fukazawa , Yasunari Nagasaki , Tatsuyuki Kawahara , Naruhiko Ichiyama , Youko Kosaka , Ayaka Mimura , Hidekazu Nakanishi , Akio Hiraki , Katsuyuki Kiura , Nagio Takigawa
{"title":"The combined inhibition of SLC1A3 and glutaminase in osimertinib-resistant EGFR mutant cells","authors":"Nobuaki Ochi ,&nbsp;Noriko Miyake ,&nbsp;Masami Takeyama ,&nbsp;Hiromichi Yamane ,&nbsp;Takuya Fukazawa ,&nbsp;Yasunari Nagasaki ,&nbsp;Tatsuyuki Kawahara ,&nbsp;Naruhiko Ichiyama ,&nbsp;Youko Kosaka ,&nbsp;Ayaka Mimura ,&nbsp;Hidekazu Nakanishi ,&nbsp;Akio Hiraki ,&nbsp;Katsuyuki Kiura ,&nbsp;Nagio Takigawa","doi":"10.1016/j.bbagen.2024.130675","DOIUrl":"10.1016/j.bbagen.2024.130675","url":null,"abstract":"<div><p>Background: We investigated the unknown mechanisms of osimertinib-resistant <em>EGFR</em>-mutant lung cancer. Methods: An osimertinib-resistant cell line (PC-9/OsmR2) was established through continuous exposure to osimertinib using an <em>EGFR</em> exon 19 deletion (19Del) lung adenocarcinoma cell line (PC-9). <em>EGFR</em> 19Del (M1), L858R/T790M/C797S (M6), and L858R/C797S (M8) expression vectors were introduced into Ba/F3 cells. A second osimertinib-resistant line (M1/OsmR) was established through continuous exposure to osimertinib using M1 cells. Results: SLC1A3 had the highest mRNA expression level in PC-9/OsmR2 compared to PC-9 cells by microarray analysis and SLC1A3 was increased by flow cytometry. In PC-9/OsmR2 cells, osimertinib sensitivity was significantly increased in combination with siSLC1A3. Because SLC1A3 functions in glutamic acid transport, osimertinib with a glutaminase inhibitor (CB-839) or an SLC1A3 inhibitor (TFB-TBOA) increased the sensitivity. Also, CB-839 plus TFB-TBOA without osimertinib resulted in greater susceptibility than did CB-839 or TFB-TBOA plus osimertinib. Comprehensive metabolome analysis showed that the M1/OsmR cells had significantly more glutamine and glutamic acid than M1 cells. CB-839 plus osimertinib exerted a synergistic effect on M6 cells and an additive effect on M8 cells. Conclusion: Targeting glutaminase and glutamic acid may overcome the osimertinib-resistant EGFR-mutant lung cancer.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765119","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
Keratinocyte and myeloid MCPIP1 have distinct roles in maintaining skin homeostasis 角质细胞和骨髓 MCPIP1 在维持皮肤稳态方面发挥着不同的作用。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2024-07-18 DOI: 10.1016/j.bbagen.2024.130671
Weronika Szukala , Agata Lichawska-Cieslar , Roza Zawada , Izabela Rumienczyk , Michal Mikula , Krzysztof Goryca , Jolanta Jura
{"title":"Keratinocyte and myeloid MCPIP1 have distinct roles in maintaining skin homeostasis","authors":"Weronika Szukala ,&nbsp;Agata Lichawska-Cieslar ,&nbsp;Roza Zawada ,&nbsp;Izabela Rumienczyk ,&nbsp;Michal Mikula ,&nbsp;Krzysztof Goryca ,&nbsp;Jolanta Jura","doi":"10.1016/j.bbagen.2024.130671","DOIUrl":"10.1016/j.bbagen.2024.130671","url":null,"abstract":"<div><p>The skin is a complex organ, and the intricate network between keratinocytes and immune cells is critical for ensuring skin function. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is a ribonuclease that functions as a key negative modulator of inflammation. We previously reported that conditional deletion of MCPIP1 in keratinocytes (Mcpip1<sup>EKO</sup>) impairs skin integrity in adult mice. A similar phenotype was observed following the depletion of MCPIP1 in the myeloid compartment (Mcpip1<sup>MKO</sup>).</p><p>The aim of this study was to develop a keratinocyte and myeloid double-MCPIP1 knockout mouse model to clarify the specific roles of myeloid and epidermal MCPIP1 in skin biology.</p><p>Histological analyses indicated that the skin morphology changed after depletion of MCPIP1 in cells of myeloid origin as well as in keratinocytes. The thicknesses of the epidermal and subcutaneous fat layers increased in the mice with a loss of epidermal MCPIP1, whereas the loss of myeloid MCPIP1 had the opposite effect. In addition, both types of mice showed opposite responses to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Transcriptomic profiling of whole-skin lysates revealed some common target transcripts in all the knockout mice. Further analyses revealed that distinct pathways are modulated following the loss of epidermal or myeloid MCPIP1. The skin morphology and inflammatory phenotype of keratinocyte and myeloid double-MCPIP1 knockout mice resembled those of mice with only keratinocyte-specific knockout of MCPIP1.</p><p>Overall, myeloid and epidermal MCPIP1 play important but distinct roles in the modulation of skin-related processes.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733474","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
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