Biochemical and biophysical research communications最新文献

{"title":"Cationic amphiphilic molecules as novel sclerosants for venous malformation treatment: A study on tranexamic acid-derived low-molecular-weight gels","authors":"Yongfeng Chen ,&nbsp;Di Song ,&nbsp;Qianqian Hou ,&nbsp;Mengrui Ma ,&nbsp;Xiaoyun Zhao ,&nbsp;Tianzhi Yang ,&nbsp;Huichao Xie ,&nbsp;Pingtian Ding","doi":"10.1016/j.bbrc.2024.150838","DOIUrl":"10.1016/j.bbrc.2024.150838","url":null,"abstract":"<div><div>Venous malformation (VM) is a prevalent congenital vascular anomaly characterized by abnormal blood vessel growth, leading to disfigurement and dysfunction. Sclerotherapy, a minimally invasive approach, has become a primary therapeutic modality for VM, but its efficacy is hampered by the rapid dilution and potential adverse effects. In this study, we introduced a series of cationic amphiphilic molecules, fatty alcohol esters (TA6, TA8, and TA9) of tranexamic acid (TA), which self-assembled into low-molecular-weight gels (LMWGs) in water. The TA9, in particular, is released slowly when hydrogel is injected into the vein locally. Then, it damages the venous wall by destroying cell membranes and precipitating proteins, causing inflammation and thrombosis, thickening of the venous wall, effectively inducing irreversible vein fibrosis. Additionally, TA9 can be rapidly degraded into TA in plasma to reduce toxicity caused by diffusion. Overall, this study suggests that the cationic amphiphilic molecule TA9 is a promising sclerosant for VM treatment, offering a novel, effective, and safe therapeutic option with potential for clinical translation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456995","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":"Scutellarin alleviated ulcerative colitis through gut microbiota-mediated cAMP/PKA/NF-κB pathway","authors":"Yang Li ,&nbsp;Mengdan Yan ,&nbsp;Miao Zhang ,&nbsp;Bo Zhang ,&nbsp;Bingzhong Xu ,&nbsp;Xu Ding ,&nbsp;Jiayu Wang ,&nbsp;Zhao Wang","doi":"10.1016/j.bbrc.2024.150837","DOIUrl":"10.1016/j.bbrc.2024.150837","url":null,"abstract":"<div><h3>Purpose</h3><div>Ulcerative colitis (UC) is a chronic, non-specific inflammatory condition of the colon, characterized by recurrent episodes and a notable lack of effective pharmacological treatments. Scutellarin, a natural component, exhibits appreciable pharmacological effects and therapeutic potential for various diseases. However, its effects on UC are not fully understood, and the precise mechanisms remain to be deciphered. This study aimed to assess the therapeutic efficacy of scutellarin and elucidate its underlying mechanisms in treating UC.</div></div><div><h3>Methods</h3><div>This study utilized dextran sulfate sodium (DSS)-induced mice to evaluate the therapeutic potential of scutellarin against UC and to elucidate the mechanisms involving the gut microbiota. An antibiotics cocktail (ABX) and fecal microbiota transplantation (FMT) were also used to determine the mechanistic role of the gut microbiota. An integrative approach combining fecal metabolomics and network pharmacology analysis was used to explore the gut microbiota-directed molecular mechanism.</div></div><div><h3>Results</h3><div>The results showed that scutellarin provided various therapeutic benefits in UC management, including alleviating weight loss, slowing disease progression, and reducing inflammatory damage in colon structures. The improved gut microbiota after scutellarin administration contributed to these effects. Fecal metabolome revealed that scutellarin selectively mitigated DSS-induced dysregulation of gut microbiota-derived metabolites, including glycolic acid, γ-aminobutyric acid, glutamate, tryptophan, xanthine, and β-hydroxypyruvate. Network pharmacology analysis, along with <em>in vivo</em> experimental verification, implicated the cAMP/PKA/NF-κB pathway in the action of these metabolites in treating UC, which may be the mechanism responsible for scutellarin's curative effects on UC.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potential of scutellarin in alleviating UC by activating the cAMP/PKA/NF-κB pathway through gut microbiota-derived metabolites, highlighting scutellarin as a promising therapeutic agent for UC.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445153","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":"Unravelling biochemical and molecular mechanism of a carboxylesterase from Dietzia kunjamensis IITR165 reveal novel activities against polyethylene terephthalate","authors":"Saurabh Singh ,&nbsp;Mohini Soni ,&nbsp;Neha Gupta ,&nbsp;Padmani Sandhu ,&nbsp;Deepali Tripathi ,&nbsp;J. Venkatesh Pratap ,&nbsp;Srikrishna Subramanian ,&nbsp;Natesan Manickam","doi":"10.1016/j.bbrc.2024.150833","DOIUrl":"10.1016/j.bbrc.2024.150833","url":null,"abstract":"<div><div>Plastics and plasticizers accumulate in the ecological niches affecting biodiversity, and human and environmental health. Bacteria degrading polyethylene terephthalate (PET) were screened and PETases involved in PET degradation were characterized. Here, we identified a carboxylesterase Dkca1 of 48.44 kDa molecular mass from <em>Dietzia kunjamensis</em> IITR165 shown to degrade amorphous PET film into bis(2-hydroxyethyl) terephthalate (BHET) and terephthalic acid (TPA) formed 64.35 μM and 35.26 μM, respectively within 96 h at 37 °C as revealed by LC-MS analysis showed significant PET hydrolase activity similar to reported PETases. SEM analysis confirms the surface erosion as cavities and holes. Dkca1 also hydrolysed BHET and dibutyl phthalate (DBP) at a concentration of 1 mM within 3 h indicating its versatility. Fluorescence quenching shows Dkca1 protein has a maximum affinity (<em>K</em>_d) towards BHET (86.55 μM) than DBP (134.2 μM). The protein demonstrated high stability under temperatures above 40 °C and at the pH range of 6.0–9.0. Moreover, Amino acid composition showed that the Dkca1 enzyme belongs to family VII carboxylesterase containing conserved catalytic triad of Ser183-Glu289-His378 with pentapeptide motif GXSAG and an oxyanion hole H103GGG106, sharing 37.47 % and 32.44 % similarity with a PET hydrolase TfCa from <em>Thermobifida fusca</em> and PAE hydrolase CarEW from <em>Bacillus</em> sp. K91, respectively. A docking study revealed that ligand PET, BHET, and DBP showed favourable binding in the catalytic pocket of the Dkca1 protein.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445095","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":"Moderate-intensity continuous training and high-intensity interval training alleviate glycolipid metabolism through modulation of gut microbiota and their metabolite SCFAs in diabetic rats","authors":"Yuxia Han ,&nbsp;Hongjiao Quan ,&nbsp;Wei Ji ,&nbsp;Qinghua Tian ,&nbsp;Xia Liu ,&nbsp;Wenfeng Liu","doi":"10.1016/j.bbrc.2024.150831","DOIUrl":"10.1016/j.bbrc.2024.150831","url":null,"abstract":"<div><div>Glucose and lipid metabolism disorders are typical of diabetic patients and are important factors leading to macrovascular and microvascular complications. The aim of this study was to understand the effects of different exercises on glycolipid metabolism in diabetic rats and the role of gut flora in metabolic maintenance. We measured glycolipid metabolic indices and short-chain fatty acids (SCFAs) content and sequenced and analyzed gut microbes after 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) programs in type 2 diabetic rats(T2DM). We found that Enterococcaceae, Enterococcus, Subdoligranulum, Kurthia, Bacillales, and Planococcaceae may be key bacterial taxa related to T2DM and that both programs of exercise regulated the intestinal flora of rats with T2DM, improved their glycolipid metabolism, increased the abundance of SCFA-producing intestinal bacteria, and it was found that the PWY-5676 and P163-PWY pathways which are closely related to production of SCFAs were significantly upregulated in the exercise groups. Notably, MICT appeared to be more effective than HIIT in increasing the homogeneity of rat intestinal flora, enriching species, and increasing acetic acid and butyric acid content. These results suggest that exercise improves glycolipid metabolism in diabetic rats, which may be attributed to alterations in the structure of their intestinal flora.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457015","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":"Shedding light on cancer immunology at the molecular level: A quantum biochemistry study of representative PD-1/PD-L1 conformations","authors":"Victor L.B. França ,&nbsp;Jackson L. Amaral ,&nbsp;Cláudia do Ó Pessoa ,&nbsp;Hernandes F. Carvalho ,&nbsp;Valder N. Freire","doi":"10.1016/j.bbrc.2024.150832","DOIUrl":"10.1016/j.bbrc.2024.150832","url":null,"abstract":"<div><h3>Background</h3><div>Programmed death 1 (PD-1) binding to PD-L1 is a potent mechanism used by immunogenic tumors to evade the immune system and the immune checkpoint PD-1PD-L1 has emerged as a promising target in the search for new drugs to improve cancer treatment. The crystallographic structure of _humanPD-1_humanPD-L1 shed light on the molecular characterization of this system and allowed computational studies to be carried out to characterize structural behaviors.</div></div><div><h3>Methods</h3><div>This study demonstrated the importance of analyzing the flexibility of protein systems through molecular dynamics simulations (MDS) and its impacts on the interaction energy obtained through quantum biochemistry.</div></div><div><h3>Results</h3><div>The computational results obtained provide a description of the flexibility and energetic profile of the PD-1PD-L1 contact surface using representative conformations from MDS. Variations of up to 50 % in the total interaction energy values were detected depending on the scrutinized conformation, which can be mainly attributed to the flexibility of the CC' loop, FG loop and ASP85-GLN91 of PD-1 and the MET58-LYS62 segment of PD-L1. Quantum biochemistry revealed the three hot spots in PD-L1: ARG113_L-ARG125_L &gt; ILE54_L-VAL76_L &gt; ALA18_L-ASP26_L; and two energetic hot spots in PD-1: ALA125-ARG139 &gt; VAL63-GLN88. Nonetheless, VAL63-GLN88 and GLY124-ARG139 exhibit significant variation in interaction energy between different conformations, while ARG113_L-ARG125_L is the only hot spot with high energetic fluctuation on the PD-L1 surface.</div></div><div><h3>Conclusion</h3><div>This is the first application of MDS coupled to dimensionality reduction and density functional theory (DFT) demonstrating new structural and energetic features that might be useful in discovering/designing more potent PD-1PD-L1 inhibitors.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445152","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":"Understanding fungal and plant active urea transport systems: Keys from Aspergillus nidulans and beyond","authors":"Ana Ramón ,&nbsp;Manuel Sanguinetti ,&nbsp;Lucianna Helene Silva Santos ,&nbsp;Sotiris Amillis","doi":"10.1016/j.bbrc.2024.150801","DOIUrl":"10.1016/j.bbrc.2024.150801","url":null,"abstract":"<div><div>Urea is present in all ecosystems, as a result of the metabolism of different organisms and also of human activity, being the world's most common form of nitrogen fertilizer. Fungi and plants can use urea as a nitrogen source, taking it up from the environment through specialized active transport proteins. These proteins belong to a subfamily of urea/H⁺ symporters included in the Solute:Sodium Symporter (SSS) family of transporters. In this review we summarize the current knowledge on this group of transporters, based on our previous studies on <em>Aspergillus nidulans</em> UreA. We delve into its transcriptional and post-translational regulation, structure-function relationships, transport mechanism, and certain aspects of its biogenesis. Recent findings suggest that this urea transporter subfamily is more expanded than originally thought, with representatives found in organisms as diverse as Archaea and mollusks, which raises questions on evolutionary aspects. <em>A. nidulans ureA</em> knockout strains provide a valuable platform for expressing urea transporters from diverse sources, facilitating their characterization and functional analysis. In this context, given the close relationship between plant and fungal active urea transporters, this knowledge could serve to develop strategies to improve the efficiency of applied urea as fertilizer.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493896","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":"Aspirin enhances radio/chemo-therapy sensitivity in C. elegans by inducing germ cell apoptosis and suppresses RAS overactivated tumorigenesis via mtROS-mediated DNA damage and MAPK pathway","authors":"Xiaona Li ,&nbsp;Feng Xu ,&nbsp;Ruru Wang ,&nbsp;Lili Shen ,&nbsp;Bowen Luo ,&nbsp;Shenglan Zhou ,&nbsp;Jie Zhang ,&nbsp;Zhaoyang Zhang ,&nbsp;Zhizun Cao ,&nbsp;Kangren Zhan ,&nbsp;Ye Zhao ,&nbsp;Guoping Zhao","doi":"10.1016/j.bbrc.2024.150828","DOIUrl":"10.1016/j.bbrc.2024.150828","url":null,"abstract":"<div><div>Previous studies have demonstrated that combination therapy involving radiotherapy and aspirin decreases the survival rate of cancer cells. However, the mechanism by which aspirin exerts its radiation sensitization effect at the in vivo level remains largely unclear. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effect of aspirin combined with radio/chemo-therapy on tumors at the individual level. Here, we illustrate that high-dose aspirin increases the expression of genes involved in core apoptosis pathways (egl-1, ced-9, ced-4 and ced-3) and induces germ cell apoptosis in C. elegans through mitochondrial outer membrane permeabilization (MOMP) and elevation of reactive oxygen species (ROS) levels. Crucially, aspirin-induces ROS upregulates the expression of genes critical for DNA damage response (hus-1, clk-2 and cep-1) and genes involved in MAPK pathways (lin-45, mek-2, mpk-1, sek-1 and pmk-1), thereby mediating the enhanced sensitivity of radio/chemo-therapy by aspirin. Notably, aspirin fails to induce germ cell apoptosis and enhance radio/chemo-therapy in C. elegans lacking the expression of each of those genes. Furthermore, in a C. elegans tumor-like symptom model, aspirin enhances radio/chemo-therapy sensitivity through ROS induction. However, low-dose aspirin can diminish the apoptotic signal of reproductive cells in C. elegans and exert anti-inflammatory effects. Our research results suggest that the tumor-suppressive and radio/chemo-therapy sensitizing effects of aspirin provide robust experimental evidence for improving the clinical efficacy of tumor radio/chemo-therapy and deepening our understanding of aspirin's mechanism of action in cancer.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445151","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":"Mitochondrial dysfunction matures Ras-induced early senescence to full senescence with a proinflammatory senescence-associated secretory phenotype in the fish cell line, EPC","authors":"Rin Shirasaka,&nbsp;Takayuki Katagiri,&nbsp;Kunihiko Futami","doi":"10.1016/j.bbrc.2024.150824","DOIUrl":"10.1016/j.bbrc.2024.150824","url":null,"abstract":"<div><div>Fish cell lines differ from most mammalian diploid cell lines by the fact that cellular senescence is not readily induced. Previously, we demonstrated that the absence of the <em>p16</em> gene in the fish genome prevents cells from reaching full senescence even when Ras is activated. <em>Drosophila</em> also lacks <em>p16</em>; however, early senescence triggered by Ras activation progresses to full senescence and is accompanied by a proinflammatory senescence-associated secretory phenotype (SASP), due to mitochondrial deficiency. It is unclear whether mitochondrial deficiency can also induce the maturation of Ras-induced early senescence (RIS) to full senescence along with a proinflammatory SASP in fish cell lines. Here, we investigated whether mitochondrial dysfunction induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in concert with activated Ras results in full senescence and whether this is accompanied by a proinflammatory SASPs in the EPC fish cell line. We found that although EPC cells with mitochondrial dysfunction exhibited a proinflammatory SASP, this did not result in permanent cell proliferation arrest or the upregulation of endogenous Ras expression. These findings suggest that other factors must act in concert with mitochondrial dysfunction to induce full senescence. The proliferation of EPC cells overexpressing a constitutively active mutant of H-Ras (H-Ras^V12) was markedly reduced, irrespective of CCCP treatment. These findings suggest that there are similarities between the cellular senescence observed in fish and <em>Drosophila</em> cells lacking the <em>p16</em> gene. However, it should be noted that fish cells differ from <em>Drosophila</em> cells in that mitochondrial dysfunction alone can induce proinflammatory SASP factors.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432717","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":"Upadacitinib counteracts hepatic lipid deposition via the repression of JAK1/STAT3 signaling and AMPK/autophagy-mediated suppression of ER stress","authors":"Sung Ho Ahn ,&nbsp;Yong-Jik Lee ,&nbsp;Do Su Lim ,&nbsp;Wonjun Cho ,&nbsp;Hyeon Ji Gwon ,&nbsp;A.M. Abd El-Aty ,&nbsp;Ji Hoon Jeong ,&nbsp;Tae Woo Jung","doi":"10.1016/j.bbrc.2024.150829","DOIUrl":"10.1016/j.bbrc.2024.150829","url":null,"abstract":"<div><div>Upadacitinib (UPA) has been utilized to treat conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis by modulating inflammation <em>via</em> the JAK pathway. However, its impact on hepatic lipogenesis remains insufficiently studied. This research evaluated protein expression through Western blotting, lipid accumulation with oil red O staining, autophagosomes in hepatocytes <em>via</em> MDC staining, and hepatic apoptosis <em>via</em> cell viability and caspase 3 activity assays. This study aimed to explore the effects of UPA on hepatic lipogenesis and the underlying molecular mechanisms in <em>in vitro</em> models of hepatic steatosis. These findings demonstrated that UPA reduced lipid deposition, apoptosis, and ER stress in palmitate-treated hepatocytes. UPA treatment inhibited phosphorylated JAK1 and STAT3 while promoting the expression of phosphorylated AMPK and autophagy markers. AMPK siRNA negated the effects of UPA on lipogenic lipid deposition, apoptosis, JAK1/STAT3 phosphorylation, and ER stress. These results reveal that UPAmitigates ER stress through the JAK1/STAT3/AMPK pathway, thereby reducing lipid deposition and apoptosis in hyperlipidemic hepatocytes, supporting its potential as a therapeutic strategy for treating hepatic steatosis in obese individuals.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433336","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":"Cholic acid activation of GPBAR1 does not induce or exacerbate acute pancreatitis but promotes exocrine pancreatic secretion","authors":"Peng An ,&nbsp;Yudan Fan ,&nbsp;Qian Wang ,&nbsp;Na Huang ,&nbsp;Haiyan Chen ,&nbsp;Jin Sun ,&nbsp;Ziwei Du ,&nbsp;Chen Zhang ,&nbsp;Jun Li","doi":"10.1016/j.bbrc.2024.150825","DOIUrl":"10.1016/j.bbrc.2024.150825","url":null,"abstract":"<div><div>Obstruction of bile ducts due to gallstones can lead to biliary acute pancreatitis (BAP). According to Perides et al., G protein-coupled bile acid receptor-1 (GPBAR1) mediates BAP. However, Zi's findings suggest that GPR39, rather than GPBAR1, mediates TLCAS-induced increases in cytosolic calcium and acinar cell necrosis, casting doubt on the role of GPBAR1 in BAP. Numerous G protein-coupled receptors on pancreatic acinar cells utilize Ca²⁺ and cyclic adenosine monophosphate (cAMP) as second messengers to manage pancreatic exocrine secretion, with significant cross-talk between these signals. The primary bile acid cholic acid (CA) and its conjugated forms are predominant in the human gallbladder. This study aimed to clarify the role and physiological significance of GPBAR1 by investigating the physiological and pathological effects of CA activation on GPBAR1 in pancreatic acinar cells. Isolated rat pancreatic acinar cells were treated with CA and CCK in vitro to observe the effect of CA-induced cAMP signaling on CCK-induced physiological and pathological calcium signaling. In vivo evaluations involved reverse biliopancreatic duct injections of 5 % sodium taurocholate (STC) or 5 % CA in rats. CA induced intracellular cAMP signaling in a concentration-dependent manner without increasing the intracellular Ca²⁺ concentration. CA did not independently cause calcium overload or enzyme activation, nor did it exacerbate calcium overload or enzyme activation from high-dose CCK. Reverse biliopancreatic duct injections of 5 % CA did not cause acute pancreatitis in the rats. Transcriptomic analysis revealed that 50 μM CA induced changes in gene expression related to protein synthesis in the endoplasmic reticulum and ribosomes. Furthermore, 50 μM CA accelerated the calcium waves and increased the enzyme secretion induced by CCK. GPBAR1 was found on the basolateral membrane in rat pancreatic tissue rather than near the apical region of acinar cells.</div><div>GPBAR1 activation is not crucial for BAP activity but may play a role in bile acid regulation of pancreatic exocrine secretion, suggesting that GPBAR1 is a potential therapeutic target for pancreatic exocrine insufficiency.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456997","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}