Biochimica et biophysica acta. Proteins and proteomics最新文献_第9页

Corrigendum to “The explorations of dynamic interactions of paxillin at the focal adhesions” [Biochimica et Biophysica Acta(BBA) - Proteins and Proteomics 1870/10 (2022) 140825] 勘误表“在局灶性粘连处探索帕罗西汀的动态相互作用”[Biochimica et Biophysica Acta（BBA）-蛋白质和蛋白质组学1870/10（2022）140825]。

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-07-01 DOI: 10.1016/j.bbapap.2023.140905

Aziz ur Rehman Aziz , Sha Deng , Yuhang Jin , Na Li , Zhengyao Zhang , Xiaohui Yu , Bo Liu

引用次数: 0

Kinetic control in amyloid polymorphism: Different agitation and solution conditions promote distinct amyloid polymorphs of alpha-synuclein 淀粉样蛋白多态性的动力学控制：不同的搅拌和溶液条件促进不同的α-突触核蛋白淀粉样蛋白多晶型

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-07-01 DOI: 10.1016/j.bbapap.2023.140917

Santosh Devi , Dushyant Kumar Garg , Rajiv Bhat

{"title":"Kinetic control in amyloid polymorphism: Different agitation and solution conditions promote distinct amyloid polymorphs of alpha-synuclein","authors":"Santosh Devi , Dushyant Kumar Garg , Rajiv Bhat","doi":"10.1016/j.bbapap.2023.140917","DOIUrl":"10.1016/j.bbapap.2023.140917","url":null,"abstract":"<div>Aggregation of neuronal protein α-synuclein is implicated in synucleinopathies, including Parkinson's disease. Despite abundant in vitro studies, the mechanism of α-synuclein assembly process remains ambiguous. In this work, α-synuclein aggregation was induced by its constant mixing in two separate modes, either by agitation in a 96-well microplate reader (MP) or in microcentrifuge tubes using a shaker incubator (SI). Aggregation in both modes occurred through a sigmoidal growth pattern with a well-defined lag, growth, and saturation phase. The end-stage MP- and SI-derived aggregates displayed distinct differences in morphological, biochemical, and spectral signatures as discerned through AFM, proteinase-K digestion, FTIR, Raman, and CD spectroscopy. The MP-derived aggregates showed irregular morphology with a significant random coil conformation, contrary to SI-derived aggregates, which showed typical β-sheet fibrillar structures. The end-stage MP aggregates convert to β-rich SI-like aggregates upon 1) seeding with SI-derived aggregates and 2) agitating in SI. We conclude that end-stage MP aggregates were in a kinetically trapped conformation, whose kinetic barrier was bypassed upon either seeding by SI-derived fibrils or shaking in SI. We further show that MP-derived aggregates that form in the presence of sorbitol, an osmolyte, displayed a β-rich signature, indicating that the preferential exclusion effect of osmolytes helped overcome the kinetic barrier. Our findings help in unravelling the kinetic origin of different α-synuclein aggregated polymorphs (strains) that encode diverse variants of synucleinopathies. We demonstrate that kinetic control shapes the polymorphic landscape of α-synuclein aggregates, both through de novo generation of polymorphs, and by their interconversion.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9649885","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

Thermodynamic modulation of folding and aggregation energy landscape by DNA binding of functional domains of TDP-43 TDP-43功能域DNA结合对折叠和聚集能量景观的热力学调节

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-07-01 DOI: 10.1016/j.bbapap.2023.140916

Divya Patni , Santosh Kumar Jha

{"title":"Thermodynamic modulation of folding and aggregation energy landscape by DNA binding of functional domains of TDP-43","authors":"Divya Patni , Santosh Kumar Jha","doi":"10.1016/j.bbapap.2023.140916","DOIUrl":"10.1016/j.bbapap.2023.140916","url":null,"abstract":"<div>TDP-43 is a vital nucleic acid binding protein which forms stress-induced aberrant aggregates in around 97% cases of ALS, a fatal neurodegenerative disease. The functional tandem RRM domain of the protein (TDP-43tRRM) has been shown to undergo amyloid-like aggregation under stress in a pH-dependent fashion. However, the underlying thermodynamic and molecular basis of aggregation and how the energy landscape of folding, stability, and aggregation are coupled and modulated by nucleic acid binding is poorly understood. Here, we show that the pH stress thermodynamically destabilizes the native protein and systematically populates the unfolded-like aggregation-prone molecules which leads to amyloid-like aggregation. We observed that specific DNA binding inhibits aggregation and populates native-like compact monomeric state even under low-pH stress as measured by circular dichroism, ANS binding, size exclusion chromatography, and transmission electron microscopy. We show that DNA-binding thermodynamically stabilizes and populates the native state even under stress and reduces the population of unfolded-like aggregation-prone molecules which leads to systematic aggregation inhibition. Our results suggest that thermodynamic modulation of the folding and aggregation energy landscape by nucleic-acid-like molecules could be a promising approach for effective therapeutic intervention in TDP-43-associated proteinopathies.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9649884","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

The molecular basis of the antidepressant action of the magic mushroom extract, psilocin 抗抑郁作用的分子基础的神奇蘑菇提取物，psilocin

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-07-01 DOI: 10.1016/j.bbapap.2023.140914

Ali Asghar Hakami Zanjani, Teresa Quynh Tram Nguyen, Luise Jacobsen, Himanshu Khandelia

{"title":"The molecular basis of the antidepressant action of the magic mushroom extract, psilocin","authors":"Ali Asghar Hakami Zanjani, Teresa Quynh Tram Nguyen, Luise Jacobsen, Himanshu Khandelia","doi":"10.1016/j.bbapap.2023.140914","DOIUrl":"10.1016/j.bbapap.2023.140914","url":null,"abstract":"<div>Magic mushrooms, and their extract psilocybin, are well-known for their psychedelic properties and recreational use. Psilocin, the bio-active form of psilocybin, can potentially treat various psychiatric diseases. Psilocin putatively exerts its psychedelic effect as an agonist to the serotonin 2A receptor (5-HT2AR), which is also the receptor for the neurological hormone serotonin. The two key chemical differences between the two molecules are first, that the primary amine in serotonin is replaced with a tertiary amine in psilocin, and second, the hydroxyl group is substituted differently on the aromatic ring. Here, we find that psilocin can bind to 5-HT2AR with an affinity higher than serotonin, and provide the molecular logic behind the higher binding affinity of psilocin using extensive molecular dynamics simulations and free energy calculations. The binding free energy of psilocin is dependent upon the protonation states of the ligands, as well as that of the key residue in the binding site: Aspartate 155. We find that the tertiary amine of psilocin, and not the altered substitution of the hydroxyl group in the ring is responsible for the increased affinity of psilocin. We propose design rules for effective antidepressants based on molecular insights from our simulations.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021774","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: 1

Comparison of force fields to study the zinc-finger containing protein NPL4, a target for disulfiram in cancer therapy 比较力场研究含锌指蛋白NPL4，二硫仑在癌症治疗中的靶点

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-07-01 DOI: 10.1016/j.bbapap.2023.140921

Simone Scrima , Matteo Tiberti , Ulf Ryde , Matteo Lambrughi , Elena Papaleo

{"title":"Comparison of force fields to study the zinc-finger containing protein NPL4, a target for disulfiram in cancer therapy","authors":"Simone Scrima , Matteo Tiberti , Ulf Ryde , Matteo Lambrughi , Elena Papaleo","doi":"10.1016/j.bbapap.2023.140921","DOIUrl":"10.1016/j.bbapap.2023.140921","url":null,"abstract":"<div>Molecular dynamics (MD) simulations are a powerful approach to studying the structure and dynamics of proteins related to health and disease. Advances in the MD field allow modeling proteins with high accuracy. However, modeling metal ions and their interactions with proteins is still challenging. NPL4 is a zinc-binding protein and works as a cofactor for p97 to regulate protein homeostasis. NPL4 is of biomedical importance and has been proposed as the target of disulfiram, a drug recently repurposed for cancer treatment. Experimental studies proposed that the disulfiram metabolites, bis-(diethyldithiocarbamate)‑copper and cupric ions, induce NPL4 misfolding and aggregation. However, the molecular details of their interactions with NPL4 and consequent structural effects are still elusive. Here, biomolecular simulations can help to shed light on the related structural details. To apply MD simulations to NPL4 and its interaction with copper the first important step is identifying a suitable force field to describe the protein in its zinc-bound states. We examined different sets of non-bonded parameters because we want to study the misfolding mechanism and cannot rule out that the zinc may detach from the protein during the process and copper replaces it. We investigated the force-field ability to model the coordination geometry of the metal ions by comparing the results from MD simulations with optimized geometries from quantum mechanics (QM) calculations using model systems of NPL4. Furthermore, we investigated the performance of a force field including bonded parameters to treat copper ions in NPL4 that we obtained based on QM calculations.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9750955","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: 1

Structural characterization of the type I-B CRISPR Cas7 from Thermobaculum terrenum 末端热杆菌I-B型CRISPR Cas7的结构表征

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-05-01 DOI: 10.1016/j.bbapap.2023.140900

Pil-Won Seo , Do-Heon Gu , Ji-Won Kim , Jun-Hong Kim , Suk-Youl Park , Jeong-Sun Kim

{"title":"Structural characterization of the type I-B CRISPR Cas7 from Thermobaculum terrenum","authors":"Pil-Won Seo , Do-Heon Gu , Ji-Won Kim , Jun-Hong Kim , Suk-Youl Park , Jeong-Sun Kim","doi":"10.1016/j.bbapap.2023.140900","DOIUrl":"10.1016/j.bbapap.2023.140900","url":null,"abstract":"<div>Clustered regularly interspaced short palindromic repeats (CRISPR) in many prokaryotes functions as an adaptive immune system against mobile genetic elements. A heterologous ribonucleoprotein silencing complex composed of CRISPR-associated (Cas) proteins and a CRISPR RNA (crRNA) neutralizes the incoming mobile genetic elements. The type I and III silencing complexes commonly include a protein-helical backbone of several copies of identical subunits, for example, Cas7 in the type I silencing complex.In this study, we structurally characterized type I-B Cas7 (Csh2 from Thermobaculum terrenum; TterCsh2). The revealed crystal structure of TterCsh2 shows a typical glove-like architecture of Cas7, which consists of a palm, a thumb, and a finger domain. Csh2 proteins have 5 conserved sequence motifs that are arranged to form a presumable crRNA-binding site in the TterCsh2 structure. This crRNA binding site of TterCsh2 is structurally and potentially comparable to those observed in helix-forming Cas7 structures in other sub-types. Analysis of the reported Cas7 structures and their sequences suggests that Cas7s can be divided into at least two sub-classes. These data will broaden our understanding on the Cascade complex of CRISPR/Cas systems.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9472083","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

Molecular dynamics simulations suggest Thiosemicarbazones can bind p53 cancer mutant R175H 分子动力学模拟表明，硫代氨基脲可以结合p53癌症突变体R175H

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-05-01 DOI: 10.1016/j.bbapap.2023.140903

Tanushree Das, Chaitali Mukhopadhyay

{"title":"Molecular dynamics simulations suggest Thiosemicarbazones can bind p53 cancer mutant R175H","authors":"Tanushree Das, Chaitali Mukhopadhyay","doi":"10.1016/j.bbapap.2023.140903","DOIUrl":"10.1016/j.bbapap.2023.140903","url":null,"abstract":"<div>Cancer pathologies are associated with the unfolding and aggregation of most recurring mutations in the DNA Binding Domain (DBD) of p53 that coordinate the destabilization of protein. Substitution at the 175th codon with arginine to histidine (R175H, a mutation of large to small side-chain amino acid) destabilizes the DBD by 3 kcal/mol and triggers breasts, lung cancer, etc. Stabilizing the p53 mutant by small molecules offers an attractive drug-targeted anti-cancer therapy. The thiosemicarbazone (TSC) molecules NPC and DPT are known to act as zinc-metallochaperones to reactivate p53R175H. Here, a combination of LESMD simulations for 10 TSC conformations with a p53R175H receptor, single ligand-protein conformation MD, and ensemble docking with multiple p53R175H conformations observed during simulations is suggested to identify the potential binding site of the target protein in light of their importance for the direct TSC – p53R175H binding. NPC binds mutant R175H in the loop region L2-L3, forming pivotal hydrogen bonds with HIS175, pi‑sulfur bonds with TYR163, and pi-alkyl linkages with ARG174 and PRO190, all of which are contiguous to the zinc-binding native site on p53DBD. DPT, on the other hand, was primarily targeting alternative binding sites such as the loop-helix L1/H2 region and the S8 strand. The similar structural characteristics of TSC-bound p53R175H complexes with wild-type p53DBD are thought to be attributable to involved interactions that favour binding free energy contributions of TSC ligands. Our findings may be useful in the identification of novel pockets with druggable properties.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114046","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

Structure of the complex of camel peptidoglycan recognition protein-S with hexanoic acid reveals novel features of the versatile ligand-binding site at the dimeric interface 骆驼肽聚糖识别蛋白s与己酸复合物的结构揭示了二聚体界面上多功能配体结合位点的新特征

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-05-01 DOI: 10.1016/j.bbapap.2022.140887

Ankit Maurya, Pradeep Sharma, Prashant K. Singh, V. Viswanathan, Punit Kaur, Sujata Sharma, Tej P. Singh

{"title":"Structure of the complex of camel peptidoglycan recognition protein-S with hexanoic acid reveals novel features of the versatile ligand-binding site at the dimeric interface","authors":"Ankit Maurya, Pradeep Sharma, Prashant K. Singh, V. Viswanathan, Punit Kaur, Sujata Sharma, Tej P. Singh","doi":"10.1016/j.bbapap.2022.140887","DOIUrl":"10.1016/j.bbapap.2022.140887","url":null,"abstract":"<div>The short peptidoglycan recognition protein (PGRP-S) of the innate immune system recognizes the invading microbes through binding to their cell wall molecules. In order to understand the mode of binding of PGRP-S to bacterial cell wall molecules, the structure of the complex of camel PGRP-S (CPGRP-S) with hexanoic acid has been determined at 2.07 Å resolution. Previously, we had reported the structures of CPGRP-S in the native unbound state as well as in the complexed forms with the components of various bacterial cell wall molecules such as peptidoglycan (PGN), lipopolysaccharide (LPS), lipoteichoic acid (LTA), mycolic acid (MA) and other fatty acids. These structures revealed that CPGRP-S formed two homodimers which were designated as A-B and C<img>D dimers. It also showed that the fatty acids bind to CPGRP-S in the binding site at the A-B dimer while the non-fatty acids were shown to bind at the interfaces of both A-B and C<img>D dimers. The present structure of the complex of CPGRP-S with hexanoic acid (HA) showed that HA binds to CPGRP-S at the interface of C<img>D dimer. HA was located in the same groove at the C<img>D interface which was occupied by non-fatty acids such as PGN, LPS and LTA and interacts with residues from both C and D molecules. HA is firmly held in the groove with several hydrogen bonds and a number of van der Waals contacts. This is the first structure which reports the binding of a fatty acid in the cleft at the interface of C<img>D dimer.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9118627","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

Analysis and prediction of protein stability based on interaction network, gene ontology, and KEGG pathway enrichment scores 基于互作网络、基因本体和KEGG通路富集评分的蛋白质稳定性分析与预测

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-05-01 DOI: 10.1016/j.bbapap.2023.140889

Feiming Huang , Minfei Fu , JiaRui Li , Lei Chen , KaiYan Feng , Tao Huang , Yu-Dong Cai

{"title":"Analysis and prediction of protein stability based on interaction network, gene ontology, and KEGG pathway enrichment scores","authors":"Feiming Huang , Minfei Fu , JiaRui Li , Lei Chen , KaiYan Feng , Tao Huang , Yu-Dong Cai","doi":"10.1016/j.bbapap.2023.140889","DOIUrl":"10.1016/j.bbapap.2023.140889","url":null,"abstract":"<div>Metabolic stability of proteins plays a vital role in various dedicated cellular processes. Traditional methods of measuring the metabolic stability are time-consuming and expensive. Therefore, we developed a more efficient computational approach to understand the protein dynamic action mechanisms in biological process networks. In this study, we collected 341 short-lived proteins and 824 non-short-lived proteins from U2OS; 342 short-lived proteins and 821 non-short-lived proteins from HEK293T; 424 short-lived proteins and 1153 non-short-lived proteins from HCT116; and 384 short-lived proteins and 992 non-short-lived proteins from RPE1. The proteins were encoded by GO and KEGG enrichment scores based on the genes and their neighbors in STRING, resulting in 20,681 GO term features and 297 KEGG pathway features. We also incorporated the protein interaction information from STRING into the features and obtained 19,247 node features. Boruta and mRMR methods were used for feature filtering, and IFS method was used to obtain the best feature subsets and create the models with the highest performance. The present study identified 42 features that did not appear in previous studies and classified them into eight groups according to their functional annotation. By reviewing the literature, we found that the following three functional groups were critical in determining the stability of proteins: synaptic transmission, post-translational modifications, and cell fate determination. These findings may serve as a valuable reference for developing drugs that target protein stability.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9118646","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: 16

Citrus flavanone metabolites significantly modulate global proteomic profile in pancreatic β-cells under high-glucose-induced metabolic stress 柑橘黄酮代谢物显著调节高糖诱导代谢应激下胰腺β细胞的整体蛋白质组学特征

IF 3.2 4区生物学

Biochimica et biophysica acta. Proteins and proteomics Pub Date : 2023-05-01 DOI: 10.1016/j.bbapap.2023.140898

Layanne Nascimento Fraga , Dragan Milenkovic , Sara Lima Anacleto , Michelle Salemi , Franco Maria Lajolo , Neuza Mariko Aymoto Hassimotto

{"title":"Citrus flavanone metabolites significantly modulate global proteomic profile in pancreatic β-cells under high-glucose-induced metabolic stress","authors":"Layanne Nascimento Fraga , Dragan Milenkovic , Sara Lima Anacleto , Michelle Salemi , Franco Maria Lajolo , Neuza Mariko Aymoto Hassimotto","doi":"10.1016/j.bbapap.2023.140898","DOIUrl":"10.1016/j.bbapap.2023.140898","url":null,"abstract":"<div>Hesperidin and narirutin are the major citrus flavanones. Several studies have associated these compounds with pancreatic β-cell survival through their capacity to reduce oxidative stress, inflammation, and inhibit apoptosis. However, the molecular mechanisms of action of flavanones in pancreatic β-cells under high-glycemic stress is still largely unknown. Therefore, this study aimed to decipher molecular mechanisms of flavanone metabolites in pancreatic β-cells treated with high glucose concentration using untargeted shotgun proteomics. We identified 569 proteins differentially expressed in cells exposed to hesperetin 7-glucuronide (H7G) and 265 in cells exposed to 3-(4′-hydroxyphenyl) propanoic acid (PA). Comparison of global proteomic profiles suggest that these metabolites could counteract changes in protein expression induced by high glucose stress. The bioinformatic analyses suggested that H7G and PA modulated the expression of proteins involved in cell adhesion, cell signaling, metabolism, inflammation, and protein processing in endoplasmic reticulum (ER) pathways. Taken together, this study suggests that H7G and PA can modulate the expression of proteins that may prevent dysfunction of pancreatic β-cells under stress induced by high glucose.</div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490314","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: 1