Biochemical and biophysical research communications最新文献

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Prolonged self-assembly of H. pylori ferritin globules at physiological conditions.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-18 DOI: 10.1016/j.bbrc.2024.151205
Margarita S Gette, Ekaterina V Laptenkova, Vsevolod V Sudarev, Yuliya A Zagryadskaya, Ivan S Okhrimenko, Sergey V Bazhenov, Ilya V Manukhov, Yury L Ryzhykau, Alexey V Vlasov
{"title":"Prolonged self-assembly of H. pylori ferritin globules at physiological conditions.","authors":"Margarita S Gette, Ekaterina V Laptenkova, Vsevolod V Sudarev, Yuliya A Zagryadskaya, Ivan S Okhrimenko, Sergey V Bazhenov, Ilya V Manukhov, Yury L Ryzhykau, Alexey V Vlasov","doi":"10.1016/j.bbrc.2024.151205","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151205","url":null,"abstract":"<p><p>One of the promising drug delivery tools is ferritin, which features high stability at a wide range of conditions and protects cargo by its spherical protein shell. We studied the self-assembly into homoglobules of ferritin from H. pylori and a chimeric protein ferritin-SUMO. We exposed the globules to pH-driven dis/reassembly and in both cases we observed two fractions during size exclusion chromatography (SEC) procedure. The higher molecular weight fraction contained fully assembled globules of ferritin and ferritin-SUMO that well coincides with literature. Interestingly, the lower molecular weight fraction contained intermediate subglobular oligomers that also formed globules, but on a time scale of hours, while being under physiological conditions. We performed biochemical characterization of this fraction and found that, in the case of ferritin, it contained almost the whole range of intermediate oligomers with different stoichiometry. In contrast, the ferritin-SUMO fraction contained only two distinct states: dimers and globules, without any other ferritin-SUMO intermediate oligomers. We built AlphaFold-derived schemes of ferritin and ferritin-SUMO self-assembly which also indicated differences in their assembly pathways. Our results could potentially open the possibility of cargo loading into ferritins at physiological conditions and improved purification of ferritin-based products if using a ferritin-SUMO modification with following cleavage of the SUMO-tag by the SUMO protease.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151205"},"PeriodicalIF":2.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876081","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
Structural and biochemical characterization of a zinc metallopeptidase from Porphyromonas gingivalis.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-18 DOI: 10.1016/j.bbrc.2024.151201
Chunyang Feng, Weili Yu, Yongliang Jiang, Rong Xia
{"title":"Structural and biochemical characterization of a zinc metallopeptidase from Porphyromonas gingivalis.","authors":"Chunyang Feng, Weili Yu, Yongliang Jiang, Rong Xia","doi":"10.1016/j.bbrc.2024.151201","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151201","url":null,"abstract":"<p><p>The pathogen Porphyromonas gingivalis contributes to the pathogenesis of periodontitis and other systemic diseases. The zinc-dependent metallopeptidase PepO is a virulence factor that plays a crucial role in the adhesion and invasion of Porphyromonas gingivalis to human cells. Here, we solved the 2.04 Å crystal structure of wild-type PepO in complex with the inhibitor phosphoramidon. The active-site pocket of PepO appears to exhibit an increased hydrophobicity and a more pronounced negative charge, highlighting distinct structural features compared to its homologs. In addition to phosphoramidon, several zinc metallopeptidase inhibitors, including thiorphan, omapatrilat, and sacubitrilat, exhibited varying degrees of inhibition on PepO enzymatic activity. Notably, the recombinant PepO showed distinct binding profiles to human fibrinogen, a characteristic that likely contributes to its role as virulence factors. These findings provide significant insights into the structural and functional mechanisms of PepO, offering a platform for the rational design of targeted inhibitors against the periodontal pathogen P. gingivalis.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151201"},"PeriodicalIF":2.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876129","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
Synthesis of galactooligosaccharides with four β-galactosidases: Structural comparison of the products by HPLC, ESI-MS and NMR.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-18 DOI: 10.1016/j.bbrc.2024.151204
Alina Botvynko, Andriy Synytsya, Ladislav Čurda
{"title":"Synthesis of galactooligosaccharides with four β-galactosidases: Structural comparison of the products by HPLC, ESI-MS and NMR.","authors":"Alina Botvynko, Andriy Synytsya, Ladislav Čurda","doi":"10.1016/j.bbrc.2024.151204","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151204","url":null,"abstract":"<p><p>Galactooligosaccharides (GOS) are lactose-derived functional ingredients applied in food products and have great potential in health protection. The conversion of lactose to GOS commonly occurs using β-galactosidases of mould, yeast and bacterial origin. The yield and structure of the resulting GOS depend on the enzyme used and the reaction conditions. This work focuses on the structural analysis of the products obtained with four commercial β-galactosidases Maxilact LGI 5000 (ML), Maxilact A4 MG (MA), Saphera 2600 L (SA) and NOLA Fit 5500 (NL) to evaluate their efficiency and specificity. HPLC, ESI-MS and NMR spectroscopy were applied to characterise the GOS preparations. GOS were separated from the reaction mixture using activated charcoal treatment. HPLC analysis confirmed that most of the monosaccharides and a part of the lactose, but also some other disaccharides, probably allolactose and 6-galactobiose, were retained by charcoal. In all the products, ESI-MS analysis detects oligosaccharides up to hexamers. NMR spectra confirmed the presence of GOS of various configurations and polymerisation degrees and evaluated the specificity of used enzymes. MA preferably forms 1,6- and 1,4-glycosidic bonds, and bacterial enzymes NL and SA also form 1,2- and 1,3- glycosidic bonds, while yeast enzyme ML cannot produce new 1,4-glycosidic bonds. The mould enzyme MA showed the highest trans-galactosylation activity, forming longer GOS oligomers than the other enzymes.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151204"},"PeriodicalIF":2.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884866","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
NELL1 variant protein (NV1) modulates hyper-inflammation, Th-1 mediated immune response, and the HIF-1α hypoxia pathway to promote healing in viral-induced lung injury.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-17 DOI: 10.1016/j.bbrc.2024.151198
Cymbeline Culiat, Dharmendra Soni, William Malkes, Mark Wienhold, Linghua Harris Zhang, Everett Henry, Magdalena Dragan, Swagata Kar, Dana Marguerite Angeles, Shannon Eaker, Roopa Biswas
{"title":"NELL1 variant protein (NV1) modulates hyper-inflammation, Th-1 mediated immune response, and the HIF-1α hypoxia pathway to promote healing in viral-induced lung injury.","authors":"Cymbeline Culiat, Dharmendra Soni, William Malkes, Mark Wienhold, Linghua Harris Zhang, Everett Henry, Magdalena Dragan, Swagata Kar, Dana Marguerite Angeles, Shannon Eaker, Roopa Biswas","doi":"10.1016/j.bbrc.2024.151198","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151198","url":null,"abstract":"<p><p>Research underscores the urgent need for technological innovations to treat lung tissue damage from viral infections and the lasting impact of COVID-19. Our study demonstrates the effectiveness of recombinant human NV1 protein in promoting a pro-healing extracellular matrix that regulates homeostasis in response to excessive tissue reactions caused by infection and injury. NV1 achieves this by calibrating multiple biological mechanisms, including reducing hyperinflammatory cytokine levels (e.g., IFN-γ, TNF-α, IL-10, and IP-10), enhancing the production of proteins involved in viral inactivation and clearance through endocytosis and phagocytosis (e.g., IL-9, IL-1α), regulating pro-clotting and thrombolytic pathways (e.g., downregulates SERPINE 1 and I-TAC during Th1-mediated inflammation), maintaining cell survival under hypoxic conditions via HIF-1α regulation through the M3K5-JNK-AP-1 and TSC2-mTOR pathways, and promoting blood vessel formation. Our findings reveal NV1 as a potential therapeutic candidate for treating severe lung injuries caused by inflammatory and hypoxic conditions from viral infections and related diseases.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151198"},"PeriodicalIF":2.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871106","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
cDTL contributes to breast cancer progression through regulating redox homeostasis via affecting the function of system xc.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-16 DOI: 10.1016/j.bbrc.2024.151196
Shengting Wang, Libing Liu, Xiaoming Li, Qian Li, Yufang Wang, Xinghua Feng
{"title":"cDTL contributes to breast cancer progression through regulating redox homeostasis via affecting the function of system xc<sup />.","authors":"Shengting Wang, Libing Liu, Xiaoming Li, Qian Li, Yufang Wang, Xinghua Feng","doi":"10.1016/j.bbrc.2024.151196","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151196","url":null,"abstract":"<p><p>Ferroptosis is a new type of cell death caused by redox imbalance mediated by iron-dependent lipid peroxidation, which is intimately linked to human disease. Circular RNA, characterized by covalently closed loop structure, has attracted much attention due to its involvement in various biological functions. However, little is known about the role of circRNA in ferroptosis. In this study, we identified cDTL (a circular RNA derived from DTL gene) as a ferroptosis-related circRNA. cDTL expression was remarkably elevated by ferroptotic stress. Knockdown of cDTL significantly inhibited breast cancer cell growth both in vitro and in vivo through promoting ferroptosis. Mechanistically, cDTL directly bound to NRF2 and BCLAF1 in the nucleus and cytoplasm, respectively, resulting in transcriptional activation and mRNA stability of SLC7A11 (the core subunit of system Xc<sup>-</sup>), thereby repressing ferroptosis via activating GSH/GPX4 axis. Moreover, cDTL was identified as a direct transcriptional target of Myc, a well-known protooncogene that is highly activated in breast cancer. More importantly, cDTL was overexpressed in human breast cancer tissues, which was associated with dismal progression-free survival and poor differentiation. In conclusion, our data suggest that cDTL is a novel regulator of ferroptosis, targeting cDTL may be a potential therapeutic strategy for breast cancer.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151196"},"PeriodicalIF":2.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871081","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
A stable rat model of high altitude pulmonary edema established by hypobaric hypoxia combined diurnal temperature fluctuation and exercise.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-16 DOI: 10.1016/j.bbrc.2024.151193
Shuyu Zhang, Ning Wang, Huiping Ma, Linlin Jing
{"title":"A stable rat model of high altitude pulmonary edema established by hypobaric hypoxia combined diurnal temperature fluctuation and exercise.","authors":"Shuyu Zhang, Ning Wang, Huiping Ma, Linlin Jing","doi":"10.1016/j.bbrc.2024.151193","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151193","url":null,"abstract":"<p><p>Hypobaric hypoxia (HH) is regarded as the main cause of high-altitude pulmonary edema (HAPE), however, the effect of diurnal temperature fluctuation and exercise has been overlooked. The aim of current study was to elucidate the role of diurnal temperature fluctuation and exercise in the development of HAPE and establish a reliable experimental rat model. Male SPF Wistar rats were assigned to control group (1400 m, 25 °C) and five model groups: Model Ⅰ group (6000 m, 25 °C), Model Ⅱ group (6000 m, 2 °C), Model Ⅲ group (6000 m, 12 °C/2 °C light/dark cycle), Model IV group (6000 m, 2 °C, and exercise) and Model V group (6000 m, 12 °C/2 °C light/dark cycle, and exercise). After exposure for 72 h, the blood and lung tissues were collected for further research. The rats in Model I group did not show signs of HAPE. Compared with Model I group, the rats in Model II and Model III groups were suffered from more damage, evidence by enhanced oxidative stress and inflammatory reaction, but still did not show signs of HAPE. Model IV and Model V could induce HAPE, display the obvious pathological changes and edema, more serious oxidative stress and inflammatory reaction in lung tissues, suggesting that the key role of exercise in the development of HAPE. The rats in the Model V group showed the best performance in terms of modeling indicators, indicating that diurnal temperature fluctuation could further aggravate the degree of lung edema. In summary, HH combined with diurnal temperature fluctuation and exercise is a stable and reliable modeling method for HAPE, which can be used for subsequent research on the prevention and treatment of HAPE.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151193"},"PeriodicalIF":2.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871077","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
Coptisine acts as a nucleolus fluorescent probe in vitro.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-15 DOI: 10.1016/j.bbrc.2024.151194
Hui Li, Shuangshuang An, Jing Li, Xiukun Cui, Mingli Wang, Fengling Yuan, Jing Zhang, Weikai Guo, Yanzhong Hu
{"title":"Coptisine acts as a nucleolus fluorescent probe in vitro.","authors":"Hui Li, Shuangshuang An, Jing Li, Xiukun Cui, Mingli Wang, Fengling Yuan, Jing Zhang, Weikai Guo, Yanzhong Hu","doi":"10.1016/j.bbrc.2024.151194","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151194","url":null,"abstract":"<p><p>Coptisine (COP) is a natural protoberberine isoquinoline alkaloid that is isolated from Coptis chinensis and exhibits a variety of pharmacological activities, such as the inhibition of tumor growth, bacterial infection, inflammation and oxidative stress. In this study, COP penetrated and produced fluorescent signals in living tumor cell lines, primary MEF cells and polyformaldehyde-fixed cells. The fluorescent signal was detected at a wavelength of 488 nm. The fluorescent signal of COP was observed predominantly in the nucleoli and colocalized with nucleolus fibrillarin and B23. The fluorescence intensity of COP was associated with tumor malignancy. Compared with cells with high fluorescent signals, cells with low fluorescent signals were highly malignant. Taken together, these data suggest that COP can function as a nucleolus probe and a probe candidate for distinguishing tumor cell malignancy.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151194"},"PeriodicalIF":2.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871083","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
Hydroxycinnamic acids mediated modulation of α-Synuclein fibrillation: Biophysical insights.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-15 DOI: 10.1016/j.bbrc.2024.151195
Tinku, Sinjan Choudhary
{"title":"Hydroxycinnamic acids mediated modulation of α-Synuclein fibrillation: Biophysical insights.","authors":"Tinku, Sinjan Choudhary","doi":"10.1016/j.bbrc.2024.151195","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151195","url":null,"abstract":"<p><p>The fibrillation of α-synuclein (α-Syn) is considered a major contributor to Parkinson's disease (PD). Recent therapeutic measures have focused on inhibiting the fibrillation of α-Syn using various small molecules. We report here the effects of two different hydroxycinnamic acids; chlorogenic acid and sinapic acid on α-Syn fibrillation and have also discussed the mechanistic insights into their mode of modulation. The fluorescence spectroscopy shows that the two hydroxycinnamic acids bind with α-Syn with moderate affinity. Molecular docking studies provide a detailed insights into binding at the residue level and isothermal titration calorimetry reveals specific interactions, like hydrogen bonding, hydrophobic interactions, and van der Waals forces involved in the binding process. Fibrillation kinetics and transmission microscopic studies demonstrated that both chlorogenic acid and sinapic acid attenuate α-Syn fibrillation in a concentration dependent manner. Circular dichroism spectroscopy shows that these compounds bind with α-Syn and delay its structural transition in β-sheet containing fibrillar structures. Both the compounds are also effective even if added after the onset of fibrillation and the fibrillar species formed in the presence of these acids are unable to induce secondary nucleation in monomeric α-Syn. Such kind of structural and mechanistic insights are extremely crucial for designing therapeutic intervention in PD and other neurodegenerative diseases.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151195"},"PeriodicalIF":2.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871089","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
Salvianolic acid C promotes renal gluconeogenesis in fibrotic kidneys through PGC1α.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-14 DOI: 10.1016/j.bbrc.2024.151174
Yufeng Xing, Di Huang, Pinglan Lin, Yijing Zhou, Dongping Chen, Chaoyang Ye, Ming Wu
{"title":"Salvianolic acid C promotes renal gluconeogenesis in fibrotic kidneys through PGC1α.","authors":"Yufeng Xing, Di Huang, Pinglan Lin, Yijing Zhou, Dongping Chen, Chaoyang Ye, Ming Wu","doi":"10.1016/j.bbrc.2024.151174","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151174","url":null,"abstract":"<p><p>Impaired renal gluconeogenesis is recently identified as a hallmark of chronic kidney disease. However, the therapeutic approach to promote renal gluconeogenesis in CKD is still lacking. We aimed to study whether Salvianolic acid C (SAC), a nature compound extracted from the traditional Chinese medicine Danshen, inhibits renal fibrosis through promotion of gluconeogenesis. TGF-β stimulated HK2 human renal epithelial cells and mice with unilateral ureteral obstruction (UUO) were used as in vitro and in vivo models to study renal fibrosis. Fibrotic and gluconeogenic changes were determined by Western blotting analysis, quantitative PCR and Masson staining. Glucose and lactate concentrations were measured in cell culture and renal tissues. We found that SAC treatment inhibits the deposition of extracellular matrix proteins and the expression of fibrotic markers such as fibronectin, N-cadherin, Vimentin, aSMA, pSmad3, and Snail in UUO kidneys or renal cells. Inhibition of these fibrotic markers by SAC treatment was associated with enhanced expression of three gluconeogenic enzymes such as PCK1, G6PC and FBP1 in renal tissues or cells. SAC increase the concentration of glucose in the supernatant of renal cells. Lactate concentration was reduced by SAC in renal tissues or cells. Pyruvate and glucose tolerance tests showed that SAC improve the impaired glucose metabolism systemically in UUO mice. Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1ɑ) was downregulated in mouse kidneys after UUO operation, which was increased by SAC treatment. Moreover, PGC1α inhibitor SR-18292 reversed the anti-fibrotic effect and pro-gluconeogenic effect caused by SAC in renal cells. In conclusion, SAC inhibits renal fibrosis through promotion of PGC1α-mediated renal gluconeogenesis.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151174"},"PeriodicalIF":2.5,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863139","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
LASP1 inhibits the formation of NETs and alleviates acute pancreatitis by stabilizing F-actin polymerization in neutrophils.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-13 DOI: 10.1016/j.bbrc.2024.151134
Siqin Zhang, Zhihao Wang, Yuyan Zhang, Xiaowu Dong, Qingtian Zhu, Chenchen Yuan, Guotao Lu, Weijuan Gong, Yawei Bi, Yaodong Wang
{"title":"LASP1 inhibits the formation of NETs and alleviates acute pancreatitis by stabilizing F-actin polymerization in neutrophils.","authors":"Siqin Zhang, Zhihao Wang, Yuyan Zhang, Xiaowu Dong, Qingtian Zhu, Chenchen Yuan, Guotao Lu, Weijuan Gong, Yawei Bi, Yaodong Wang","doi":"10.1016/j.bbrc.2024.151134","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151134","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil extracellular traps (NETs) play a significant role in the development of acute pancreatitis (AP). The actin-binding protein LASP1 regulates proteins associated with the cytoskeleton, yet its precise involvement in NETs and AP remains to be elucidated.</p><p><strong>Methods: </strong>To investigate the role of LASP1 in NETs and AP, several bioinformatics methods, such as weighted gene co-expression network analysis (WGCNA), differential analysis, and least absolute shrinkage and selection operator (LASSO) regression, were utilized to screen for feature genes based on the Gene Expression Omnibus (GEO) dataset. To further assess the impact of LASP1, both an in vitro model of 12-myristic-13-acetate phobolol (PMA)-induced NETs and a caerulein-induced AP model were employed.</p><p><strong>Results: </strong>Through WGCNA, AP-related module genes were screened, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted to identify enriched pathways and functions. Six characteristic genes were identified through LASSO regression screening, with LASP1 being the most distinct. LASP1 reduces the generation of NETs induced by PMA in vitro. Mechanistically, LASP1 may increase F-actin protein levels by inhibiting the depolymerization of F-actin. Furthermore, our study utilizing a mouse AP model demonstrated that the LSAP1 recombinant protein effectively alleviated pancreatic necrosis in mice afflicted with AP.</p><p><strong>Conclusion: </strong>LASP1 inhibits the formation of NETs and may alleviate AP by increasing the level of F-actin protein.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151134"},"PeriodicalIF":2.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871100","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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