BiochimiePub Date : 2024-03-26DOI: 10.1016/j.biochi.2024.03.014
Maria M. Oliveira , Sofia Correia , Cecilia Peirone , Marques Magalhães , Paula Oliveira , Francisco Peixoto
{"title":"Impact of ozone therapy on mouse liver mitochondrial function and antioxidant system","authors":"Maria M. Oliveira , Sofia Correia , Cecilia Peirone , Marques Magalhães , Paula Oliveira , Francisco Peixoto","doi":"10.1016/j.biochi.2024.03.014","DOIUrl":"10.1016/j.biochi.2024.03.014","url":null,"abstract":"<div><p>Ozone therapy's efficacy might stem from the regulated and mild oxidative stress resulting from ozone's interactions with various biological elements. The present work aimed to characterize the hepatic mitochondrial response to ozone treatment and its relationship with the antioxidant system response. Two groups of mice were used: one control group and another injected intraperitoneally with an O<sub>3</sub>/O<sub>2</sub> mixture (80 ml/kg) for 5 days. Mitochondrial respiration supported by different substrates was significantly inhibited, as well as complexes I and II/III, but not complex IV. The analysis of the electron transport chain complex activity showed significant inhibitions in complexes I and II/III but not in complex IV. These inhibitions can prevent mitochondrial reactive oxygen species (ROS) production. Additionally, there was a decline in glutathione content, unaccompanied by a rise in its oxidized form. The ozone-treated groups showed a significant increase in the activity of superoxide dismutase and glutathione peroxidase, while catalase and glutathione reductase experienced no significant alterations. Adenine nucleotides increased in the ozone group, but only the increase in adenosine diphosphate is significant, so the cell's energy charge is unaffected. This study shows that mitochondria may play a crucial role in ozone treatment. However, it also highlights the need for further studies to understand the molecular mechanism.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 116-124"},"PeriodicalIF":3.9,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000725/pdfft?md5=ec8fe957fe9a87be5067c6dab43ed873&pid=1-s2.0-S0300908424000725-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320056","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}
BiochimiePub Date : 2024-03-26DOI: 10.1016/j.biochi.2024.03.016
Samuel Barbosa , Mafalda Barbosa Pedrosa , Rita Ferreira , Daniel Moreira-Gonçalves , Lúcio Lara Santos
{"title":"The impact of chemotherapy on adipose tissue remodeling: The molecular players involved in this tissue wasting","authors":"Samuel Barbosa , Mafalda Barbosa Pedrosa , Rita Ferreira , Daniel Moreira-Gonçalves , Lúcio Lara Santos","doi":"10.1016/j.biochi.2024.03.016","DOIUrl":"10.1016/j.biochi.2024.03.016","url":null,"abstract":"<div><p>The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models. To address this knowledge gap, a comprehensive narrative review was conducted. The findings underscore that chemotherapy serves as a key factor in inducing AT loss, exacerbating cachexia, a paraneoplastic syndrome that significantly compromises patient quality of life and survival. The mechanism driving AT loss appears intricately linked to alterations in AT metabolic remodeling, marked by heightened lipolysis and fatty acid oxidation, coupled with diminished lipogenesis. However, adipocyte stem cells' lost ability to divide due to chemotherapy also appears to be at the root of the loss of AT. Notably, chemotherapy seems to deactivate the mitochondrial antioxidant system by reducing key regulatory enzymes responsible for neutralizing reactive oxygen species (ROS), thereby impeding lipogenesis. Despite FDG-PET evidence of AT browning, no molecular evidence of thermogenesis was reported. Prospective investigations unraveling the molecular mechanisms modulated in AT by chemotherapy, along with therapeutic strategies aimed at preventing AT loss, promise to refine treatment paradigms and enhance patient outcomes.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 1-12"},"PeriodicalIF":3.9,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000749/pdfft?md5=058b3ddc3df668c738a551bf6c562da4&pid=1-s2.0-S0300908424000749-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308294","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":"Inhibition of soluble epoxide hydrolase as a therapeutic approach for blood-brain barrier dysfunction","authors":"Shuo Li, Huijia Song, Yanping Sun, Yongjun Sun, Huimin Zhang, Zibin Gao","doi":"10.1016/j.biochi.2024.03.015","DOIUrl":"10.1016/j.biochi.2024.03.015","url":null,"abstract":"<div><p>The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases. EpFAs play a protective role in the central nervous system via preventing neuroinflammation, making sEH a potential therapeutic target for CNS diseases. Recent studies showed that sEH inhibition prevented BBB impairment caused by stroke, hemorrhage, traumatic brain injury, hyperglycemia and sepsis via regulating the expression of tight junctions. In this review, the protective actions of sEH inhibition on BBB and potential mechanisms are summarized, and some important questions that remain to be resolved are also addressed.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"223 ","pages":"Pages 13-22"},"PeriodicalIF":3.9,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295548","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}
BiochimiePub Date : 2024-03-18DOI: 10.1016/j.biochi.2024.03.010
Jean A. Boutin , Valérie Hamon de Almeida , Nathalie Coussay , Céline Legros , Gilles Ferry , Karine Reybier
{"title":"Melatonin facts: Melatonin lacks immuno-inflammation boosting capacities at the molecular and cellular levels","authors":"Jean A. Boutin , Valérie Hamon de Almeida , Nathalie Coussay , Céline Legros , Gilles Ferry , Karine Reybier","doi":"10.1016/j.biochi.2024.03.010","DOIUrl":"10.1016/j.biochi.2024.03.010","url":null,"abstract":"<div><p>Among the properties melatonin is claimed to possess, are the immuno-inflammation inductive capacities that would be responsible of some of the paramount of activities melatonin is reported to have in most of the human pathological conditions. In the present paper, we measured the effect of melatonin on established cellular models of immuno-inflammation, and found none. The discrepancies are discussed, especially because those properties are reported at pharmacological concentration (1 μM and beyond) at which the melatonin receptors are desensitized by internalization, leading to putative non-receptor-dependent mechanism of action.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 195-202"},"PeriodicalIF":3.9,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178220","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}
BiochimiePub Date : 2024-03-16DOI: 10.1016/j.biochi.2024.03.009
{"title":"The mutual and dynamic role of TSPO and ligands in their binding process: An example with PK-11195","authors":"","doi":"10.1016/j.biochi.2024.03.009","DOIUrl":"10.1016/j.biochi.2024.03.009","url":null,"abstract":"<div><p>Translocator protein (TSPO) is an 18 kDa transmembrane protein, localized primarily on the outer mitochondrial membrane. It has been found to be involved in various physiological processes and pathophysiological conditions. Though studies on its structure have been performed only recently, there is little information on the nature of dynamics and doubts about some structures referenced in the literature, especially the NMR structure of mouse TSPO. In the present work, we thoroughly study the dynamics of mouse TSPO protein by means of atomistic molecular dynamics simulations, in presence as well as in absence of the diagnostic ligand PKA. We considered two starting structures: the NMR structure and a homology model (HM) generated on the basis of X-ray structures from bacterial TSPO. We examine the conformational landscape in both the modes for both starting points, in presence and absence of the ligand, in order to measure its impact for both structures. The analysis highlights high flexibility of the protein globally, but NMR simulations show a surprisingly flexibility even in the presence of the ligand. Interestingly, this is not the case for HM calculations, to the point that the ligand seems not so stable as in the NMR system and an unbinding event process is partially sampled. All those results tend to show that the NMR structure of mTSPO seems not deficient but is just in another portion of the global conformation space of TSPO.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"224 ","pages":"Pages 29-40"},"PeriodicalIF":3.3,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424000671/pdfft?md5=b7784e0a84b2e69202dea04a8e4b84c0&pid=1-s2.0-S0300908424000671-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144834","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}
BiochimiePub Date : 2024-03-15DOI: 10.1016/j.biochi.2024.03.006
Tatiana A. Filippova , Rami A. Masamrekh , Yulia Yu. Khudoklinova , Victoria V. Shumyantseva , Alexey V. Kuzikov
{"title":"The multifaceted role of proteases and modern analytical methods for investigation of their catalytic activity","authors":"Tatiana A. Filippova , Rami A. Masamrekh , Yulia Yu. Khudoklinova , Victoria V. Shumyantseva , Alexey V. Kuzikov","doi":"10.1016/j.biochi.2024.03.006","DOIUrl":"10.1016/j.biochi.2024.03.006","url":null,"abstract":"<div><p>We discuss the diverse functions of proteases in the context of their biotechnological and medical significance, as well as analytical approaches used to determine the functional activity of these enzymes. An insight into modern approaches to studying the kinetics and specificity of proteases, based on spectral (absorption, fluorescence), mass spectrometric, immunological, calorimetric, and electrochemical methods of analysis is given. We also examine in detail electrochemical systems for determining the activity and specificity of proteases. Particular attention is given to exploring innovative electrochemical systems based on the detection of the electrochemical oxidation signal of amino acid residues, thereby eliminating the need for extra redox labels in the process of peptide synthesis. In the review, we highlight the main prospects for the further development of electrochemical systems for the study of biotechnologically and medically significant proteases, which will enable the miniaturization of the analytical process for determining the catalytic activity of these enzymes.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 169-194"},"PeriodicalIF":3.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144833","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}
BiochimiePub Date : 2024-03-15DOI: 10.1016/j.biochi.2024.03.004
Farid Nasiri , Parisa Ebrahimi , Mohammad Bagher Shahsavani , Anis Barati , Issa Zarei , Jun Hong , Masaru Hoshino , Ali Akbar Moosavi-Movahedi , Reza Yousefi
{"title":"Unraveling the impact of the p.R107L mutation on the structure and function of human αB-Crystallin: Implications for cataract formation","authors":"Farid Nasiri , Parisa Ebrahimi , Mohammad Bagher Shahsavani , Anis Barati , Issa Zarei , Jun Hong , Masaru Hoshino , Ali Akbar Moosavi-Movahedi , Reza Yousefi","doi":"10.1016/j.biochi.2024.03.004","DOIUrl":"10.1016/j.biochi.2024.03.004","url":null,"abstract":"<div><p>To date, several pathogenic mutations have been identified in the primary structure of human α-Crystallin, frequently involving the substitution of arginine with a different amino acid. These mutations can lead to the incidence of cataracts and myopathy. Recently, an important cataract-associated mutation has been reported in the functional α-Crystallin domain (ACD) of human αB-Crystallin protein, where arginine 107 (R107) is replaced by a leucine. In this study, we investigated the structure, chaperone function, stability, oligomerization, and amyloidogenic properties of the p.R107L human αB-Crystallin using a number of different techniques. Our results suggest that the p.R107L mutation can cause significant changes in the secondary, tertiary, and quaternary structures of αB-Crystallin. This cataractogenic mutation led to the formation of protein oligomers with larger sizes than the wild-type protein and reduced the chemical and thermal stability of the mutant chaperone. Both fluorescence and microscopic assessments indicated that this mutation significantly altered the amyloidogenic properties of human αB-Crystallin. Furthermore, the mutant protein indicated an attenuated <em>in vitro</em> chaperone activity. The molecular dynamics (MD) simulation confirmed the experimental results and indicated that p.R107L mutation could alter the proper conformation of human αB-Crystallin dimers. In summary, our results indicated that the p.R107L mutation could promote the formation of larger oligomers, diminish the stability and chaperone activity of human αB-Crystallin, and these changes, in turn, can play a crucial role in the development of cataract disorder.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 151-168"},"PeriodicalIF":3.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144835","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":"The molecular crosstalk of the hippo cascade in breast cancer: A potential central susceptibility","authors":"Sulfath Thottungal Parambil, Gisha Rose Antony, Ajeesh Babu Littleflower, Lakshmi Subhadradevi","doi":"10.1016/j.biochi.2024.03.008","DOIUrl":"10.1016/j.biochi.2024.03.008","url":null,"abstract":"<div><p>The incidence of breast cancer is perpetually growing globally, and it remains a major public health problem and the leading cause of mortality in women. Though the aberrant activities of the Hippo pathway have been reported to be associated with cancer, constructive knowledge of the pathway connecting the various elements of breast cancer remains to be elucidated. The Hippo transducers, yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ), are reported to be either tumor suppressors, oncogenes, or independent prognostic markers in breast cancer. Thus, there is further need for an explicative evaluation of the dilemma with this molecular contribution of Hippo transducers in modulating breast malignancy. In this review, we summarize the intricate crosstalk of the Hippo pathway in different aspects of breast malignancy, including stem-likeness, cellular signaling, metabolic adaptations, tumor microenvironment, and immune responses. The collective data shows that Hippo transducers play an indispensable role in mammary tumor formation, progression, and dissemination. However, the cellular functions of YAP/TAZ in tumorigenesis might be largely dependent on the mechanical and biophysical cues they interact with, as well as on the cell phenotype. This review provides a glimpse into the plausible biological contributions of the cascade to the inward progression of breast carcinoma and suggests potential therapeutic prospects.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 132-150"},"PeriodicalIF":3.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144832","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}
BiochimiePub Date : 2024-03-06DOI: 10.1016/j.biochi.2024.02.011
Maria Monticelli , Bruno Hay Mele , Demi Marie Wright , Simone Guerriero , Giuseppina Andreotti , Maria Vittoria Cubellis
{"title":"Exploring ligand interactions with human phosphomannomutases using recombinant bacterial thermal shift assay and biochemical validation","authors":"Maria Monticelli , Bruno Hay Mele , Demi Marie Wright , Simone Guerriero , Giuseppina Andreotti , Maria Vittoria Cubellis","doi":"10.1016/j.biochi.2024.02.011","DOIUrl":"10.1016/j.biochi.2024.02.011","url":null,"abstract":"<div><p>PMM2-CDG, a disease caused by mutations in phosphomannomutase-2, is the most common congenital disorder of glycosylation. Yet, it still lacks a cure. Targeting phosphomannomutase-2 with pharmacological chaperones or inhibiting the phosphatase activity of phosphomannomutase-1 to enhance intracellular glucose-1,6-bisphosphate have been proposed as therapeutical approaches.</p><p>We used Recombinant Bacterial Thermal Shift Assay to assess the binding of a substrate analog to phosphomannomutase-2 and the specific binding to phosphomannomutase-1 of an FDA-approved drug - clodronate. We also deepened the clodronate binding by enzyme activity assays and <em>in silico</em> docking. Our results confirmed the selective binding of clodronate to phosphomannomutase-1 and shed light on such binding.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"222 ","pages":"Pages 123-131"},"PeriodicalIF":3.9,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030090842400049X/pdfft?md5=3d4e1ffa2e9f2fa432974a1e9e45362e&pid=1-s2.0-S030090842400049X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140056835","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}