Biochimie最新文献

{"title":"Short-term exposure to cigarette smoke upregulates cathepsin S and alters expression of tight junction ZO-1","authors":"","doi":"10.1016/j.biochi.2024.03.005","DOIUrl":"10.1016/j.biochi.2024.03.005","url":null,"abstract":"<div><div>A long-term exposure to cigarette smoke (CS) alters the integrity of airway epithelial barrier, contributes to lung dysfunction, and elicits the expression and activity of lung cathepsin S<span><span> (CatS), a cysteine protease that participates in the remodeling of connective tissue and </span>cell junctions<span>. Here, we observed that a short-term (4 days) exposure of mice to CS increased the expression and activity of CatS, while the expression level of zonula occludens 1 (ZO-1), an epithelial tight junction protein that stabilizes barrier assembly, was reduced in lung tissue lysates. Present data support that proteolytically active CatS may contribute to the defect of ZO-1 in CS-exposed mice.</span></span></div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 29-34"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substrate specificity profiling of heat-sensitive serine protease from the fungus Onygena corvina","authors":"","doi":"10.1016/j.biochi.2024.07.002","DOIUrl":"10.1016/j.biochi.2024.07.002","url":null,"abstract":"<div><div><span><span>Proteases<span> catalyze hydrolysis of </span></span>amide<span> bonds within peptides and proteins, therefore they play crucial functions for organism functioning, but also in industry to facilitate numerous processes. Feather-degrading fungus </span></span><em>Onygena corvina (O. corvina)</em><span><span> is loaded with numerous proteases that can be utilized for variety of applications. The most active species of these enzymes is heat-sensitive </span>serine protease (NHSSP), from </span><em>O. corvina</em><span> fungi and due to its potential applications in industry is an alternative to proteinase K. The uniqueness of NHSSP relies on the ability of this enzyme to hydrolyze peptides at neutral to acidic pH values between 5.0 and 8.5, with an optimum of 6.8 and a temperature activity ranging from 15 to 50 °C making NHSSP exceptionally universal enzyme.</span></div><div><span>Thus, we have performed the in-depth characterization of NHSSP substrate specificity by using a positional scanning substrate </span>combinatorial library (PS-SCL). Afterward, we obtained a set of fluorescent substrates hydrolyzed by NHSSP that served as a leading sequence for the first tailored covalent inhibitor of this enzyme, containing a diphenylphosphonate as a warhead and MeOSuc amine protecting group. Our first inhibitor for NHSSP binds potently with target protease and is a tool for future study of this enzyme functions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 91-98"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compensational role between cathepsins","authors":"","doi":"10.1016/j.biochi.2024.04.010","DOIUrl":"10.1016/j.biochi.2024.04.010","url":null,"abstract":"<div><div>Cathepsins, a family of lysosomal peptidases, play a crucial role in maintaining cellular homeostasis by regulating protein turnover and degradation as well as many specific regulatory actions that are important for proper cell function and human health. Alterations in the activity and expression of cathepsins have been observed in many diseases such as cancer, inflammation, neurodegenerative disorders, bone remodelling-related conditions and others. These changes are not exclusively harmful, but rather appear to be a compensatory response on the lack of one cathepsin in order to maintain tissue integrity. The upregulation of specific cathepsins in response to the inhibition or dysfunction of other cathepsins suggests a fine-tuned system of proteolytic balance and understanding the compensatory role of cathepsins may improve therapeutic potential of cathepsin's inhibitors. Selectively targeting one cathepsin or modulating their activity could offer new treatment strategies for a number of diseases. This review emphasises the need for comprehensive research into cathepsin biology in the context of disease. The identification of the specific cathepsins involved in compensatory responses, the elucidation of the underlying molecular mechanisms and the development of targeted interventions could lead to innovative therapeutic approaches.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 62-76"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779640","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}

{"title":"Matrix metalloproteinase landscape in the imiquimod-induced skin inflammation mouse model","authors":"","doi":"10.1016/j.biochi.2024.03.011","DOIUrl":"10.1016/j.biochi.2024.03.011","url":null,"abstract":"<div><div>Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically applied IMQ provokes local skin inflammation. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics. Our findings reveal a significant increase in the abundance of MMP-2, MMP-7, MMP-8, and MMP-13 after treatment with IMQ compared to the control skin, while MMP-3, MMP-9, and MMP-10 were exclusively detected in the IMQ-treated skin. The increased abundance and broader representation of MMPs in the IMQ-treated skin provide valuable insight into the pathophysiology of skin inflammation in the IMQ model, adding to previous studies on cytokine levels using conventional immunochemical methods. Specifically, the changes in the MMP profiles observed in the IMQ-treated skin resemble the MMP patterns found in skin lesions of individuals with psoriasis. Ultimately, the differences in MMP abundance under IMQ-induced inflammation as compared to non-inflamed control skin can be exploited as a model to investigate drug efficacy or performance of drug delivery systems.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 99-106"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186583","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}

{"title":"Cysteine cathepsins: From diagnosis to targeted therapy of cancer","authors":"Ana Ercegovič Rot ,&nbsp;Matija Hrovatin ,&nbsp;Bor Bokalj ,&nbsp;Ernestina Lavrih ,&nbsp;Boris Turk","doi":"10.1016/j.biochi.2024.09.001","DOIUrl":"10.1016/j.biochi.2024.09.001","url":null,"abstract":"<div><div>Cysteine cathepsins are a fascinating group of proteolytic enzymes that play diverse and crucial roles in numerous biological processes, both in health and disease. Understanding these proteases is essential for uncovering novel insights into the underlying mechanisms of a wide range of disorders, such as cancer. Cysteine cathepsins influence cancer biology by participating in processes such as extracellular matrix degradation, angiogenesis, immune evasion, and apoptosis. In this comprehensive review, we explore foundational research that illuminates the diverse and intricate roles of cysteine cathepsins as diagnostic markers and therapeutic targets for cancer. This review aims to provide valuable insights into the clinical relevance of cysteine cathepsins and explore their capacity to advance personalised and targeted medical interventions in oncology.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 10-28"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156933","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}

{"title":"Advances in nuclear proteostasis of metazoans","authors":"","doi":"10.1016/j.biochi.2024.04.006","DOIUrl":"10.1016/j.biochi.2024.04.006","url":null,"abstract":"<div><div>The proteostasis network and associated protein quality control (PQC) mechanisms ensure proteome functionality and are essential for cell survival. A distinctive feature of eukaryotic cells is their high degree of compartmentalization, requiring specific and adapted proteostasis networks for each compartment. The nucleus, essential for maintaining the integrity of genetic information and gene transcription, is one such compartment. While PQC mechanisms have been investigated for decades in the cytoplasm and the endoplasmic reticulum, our knowledge of nuclear PQC pathways is only emerging. Recent developments in the field have underscored the importance of spatially managing aberrant proteins within the nucleus. Upon proteotoxic stress, misfolded proteins and PQC effectors accumulate in various nuclear membrane-less organelles. Beyond bringing together effectors and substrates, the biophysical properties of these organelles allow novel PQC functions. In this review, we explore the specificity of the nuclear compartment, the effectors of the nuclear proteostasis network, and the PQC roles of nuclear membrane-less organelles in metazoans.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 148-164"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140765106","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}

{"title":"A yummy blend of homeostasis and proteolytic mechanisms","authors":"Chahrazade El Amri (Prof.),&nbsp;Dr. Carmela Giglione,&nbsp;Gilles Lalmanach (Prof.)","doi":"10.1016/j.biochi.2024.10.005","DOIUrl":"10.1016/j.biochi.2024.10.005","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 1-3"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of MG132 induced-proteotoxic stress on αB-crystallin and desmin phosphorylation and O-GlcNAcylation and their partition towards cytoskeleton","authors":"","doi":"10.1016/j.biochi.2024.04.004","DOIUrl":"10.1016/j.biochi.2024.04.004","url":null,"abstract":"<div><div><span>Small Heat Shock Proteins are considered as the first line of defense when </span>proteostasis<span><span><span> fails. Among them, αB-crystallin is expressed in striated muscles in which it interacts with </span>desmin </span>intermediate filaments<span> to stabilize them, maintaining cytoskeleton's integrity and muscular functionalities. Desmin is a key actor for muscle health; its targeting by αB-crystallin is thus crucial, especially in stress conditions.</span></span></div><div><span>αB-crystallin is phosphorylated and O-GlcNAcylated. Its phosphorylation increases consecutively to various stresses, correlated with its recruitment for cytoskeleton's safeguarding. However, phosphorylation as unique signal for cytoskeleton translocation remains controversial; indeed, O-GlcNAcylation was also proposed to be involved. Thus, there are still some gaps for a deeper comprehension of how αB-crystallin functions are finely regulated by post-translational modifications. Furthermore, </span>desmin<span> also bears both post-translational modifications; while desmin phosphorylation is closely linked to desmin intermediates filaments turnover, it is unclear whereas its O-GlcNAcylation could impact its proper function.</span></div><div>In the herein paper, we aim at identifying whether phosphorylation and/or O-GlcNAcylation are involved in αB-crystallin targeting towards cytoskeleton in proteotoxic stress induced by proteasome<span><span> inhibition in C2C12 </span>myotubes<span>. We demonstrated that proteotoxicity led to αB-crystallin's phosphorylation and O-GlcNAcylation patterns changes, both presenting a dynamic interplay depending on protein subfraction. Importantly, both post-translational modifications showed a spatio-temporal variation correlated with αB-crystallin translocation towards cytoskeleton. In contrast, we did not detect any change of desmin phosphorylation and O-GlcNAcylation. All together, these data strongly support that αB-crystallin phosphorylation/O-GlcNAcylation interplay rather than changes on desmin is a key regulator for its cytoskeleton translocation, preserving it towards stress.</span></span></div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 121-135"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-terminal processing by dipeptidyl peptidase 9: Cut and Go!","authors":"","doi":"10.1016/j.biochi.2024.03.002","DOIUrl":"10.1016/j.biochi.2024.03.002","url":null,"abstract":"<div><div>Dipeptidyl peptidase 9 (DPP9) is an intracellular amino-dipeptidase with physiological roles in the immune system, DNA repair and mitochondria homeostasis, while its deregulation is linked to cancer progression and immune-associated defects. Through its rare ability to cleave a peptide bond following the imino-acid proline, DPP9 acts as a molecular switch that regulates key proteins, such as the tumor-suppressor BRCA2. In this review we will discuss key concepts underlying the outcomes of protein processing by DPP9, including substrate turn-over by the N-degron pathway. Additionally, we will review non-enzymatic roles and the regulation of DPP9 by discussing the interactome of this protease, which includes SUMO1, Filamin A, NLRP1 and CARD8.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 180-192"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095321","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}

{"title":"Mitochondrial proteases modulate mitochondrial stress signalling and cellular homeostasis in health and disease","authors":"","doi":"10.1016/j.biochi.2024.06.005","DOIUrl":"10.1016/j.biochi.2024.06.005","url":null,"abstract":"<div><div>Maintenance of mitochondrial homeostasis requires a plethora of coordinated quality control and adaptations’ mechanisms in which mitochondrial proteases play a key role. Their activation or loss of function reverberate beyond local mitochondrial biochemical and metabolic remodelling into coordinated cellular pathways and stress responses that feedback onto the mitochondrial functionality and adaptability. Mitochondrial proteolysis modulates molecular and organellar quality control, metabolic adaptations, lipid homeostasis and regulates transcriptional stress responses. Defective mitochondrial proteolysis results in disease conditions most notably, mitochondrial diseases, neurodegeneration and cancer. Here, it will be discussed how mitochondrial proteases and mitochondria stress signalling impact cellular homeostasis and determine the cellular decision to survive or die, how these processes may impact disease etiopathology, and how modulation of proteolysis may offer novel therapeutic strategies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"226 ","pages":"Pages 165-179"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437910","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}