Biochemical and biophysical research communications最新文献

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Dapagliflozin increased pancreatic beta cell proliferation and insulinogenic index in mice fed a high-fat and high-sodium chloride diet

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-20 DOI: 10.1016/j.bbrc.2025.151364

Tomonori Hirose , Hiroshi Takagi , Mitsuhiro Kuno , Tomoyuki Sasaki , Keigo Taki , Yoshihiro Ito , Takashi Miyata , Tomoko Kobayashi , Mariko Sugiyama , Takeshi Onoue , Daisuke Hagiwara , Shintaro Iwama , Hidetaka Suga , Ryoichi Banno , Hiroshi Arima

People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion—rather than insulin resistance—is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS + Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.

{"title":"Dapagliflozin increased pancreatic beta cell proliferation and insulinogenic index in mice fed a high-fat and high-sodium chloride diet","authors":"Tomonori Hirose , Hiroshi Takagi , Mitsuhiro Kuno , Tomoyuki Sasaki , Keigo Taki , Yoshihiro Ito , Takashi Miyata , Tomoko Kobayashi , Mariko Sugiyama , Takeshi Onoue , Daisuke Hagiwara , Shintaro Iwama , Hidetaka Suga , Ryoichi Banno , Hiroshi Arima","doi":"10.1016/j.bbrc.2025.151364","DOIUrl":"10.1016/j.bbrc.2025.151364","url":null,"abstract":"<div><div>People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion—rather than insulin resistance—is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS + Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151364"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036176","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}

引用次数: 0

SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-20 DOI: 10.1016/j.bbrc.2025.151365

Jing Li , Hui Liu , Yutong Jia , Xiayidanmu Tuniyazi , Xia Liao , Jinlong Zhao , Yun Du , Ziyi Fang , Guodong Lü

Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined. Thus, this study focused on exploring the therapeutic impacts and mechanisms of SW033291 on liver damage by establishing models of APAP-induced acute liver injury in mice. The results showed that treatment with SW033291 reduces serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, decreases the area of hepatic necrosis, increases glutathione (GSH) levels, and decreases tissue malondialdehyde (MDA) content, as well as the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in mice with liver injury. It could also promote hepatocyte proliferation and inhibit apoptosis by increasing tissue prostaglandin E2 (PGE2) levels. In conclusion, SW033291 demonstrates the capacity to ameliorate APAP-induced hepatic injury in mice by fostering liver regeneration, attenuating oxidative stress, and modulating inflammatory responses, thereby presenting itself as a promising candidate for the development of therapeutic interventions targeting acute liver failure.

对乙酰氨基酚（APAP）是一种常用的解热镇痛药。过量服用 APAP 是导致药物性肝损伤和急性肝衰竭（ALF）的主要原因。SW033291 已被证明在多种疾病的组织再生中发挥作用；然而，它在 APAP 引起的肝损伤后促进肝再生的潜力仍未得到研究。因此，本研究通过建立 APAP 诱导的小鼠急性肝损伤模型，重点探索 SW033291 对肝损伤的治疗作用和机制。结果显示，用 SW033291 治疗可降低血清丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）活性，减少肝坏死面积，增加谷胱甘肽（GSH）水平，降低组织丙二醛含量、还能降低肝损伤小鼠组织中丙二醛（MDA）的含量以及肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达水平。它还能通过增加组织中前列腺素 E2（PGE2）的水平来促进肝细胞增殖和抑制肝细胞凋亡。总之，SW033291 能够通过促进肝脏再生、减轻氧化应激和调节炎症反应来改善 APAP 引起的小鼠肝损伤，因此有望成为开发针对急性肝衰竭的治疗干预措施的候选药物。

{"title":"SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice","authors":"Jing Li , Hui Liu , Yutong Jia , Xiayidanmu Tuniyazi , Xia Liao , Jinlong Zhao , Yun Du , Ziyi Fang , Guodong Lü","doi":"10.1016/j.bbrc.2025.151365","DOIUrl":"10.1016/j.bbrc.2025.151365","url":null,"abstract":"<div><div>Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined. Thus, this study focused on exploring the therapeutic impacts and mechanisms of SW033291 on liver damage by establishing models of APAP-induced acute liver injury in mice. The results showed that treatment with SW033291 reduces serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, decreases the area of hepatic necrosis, increases glutathione (GSH) levels, and decreases tissue malondialdehyde (MDA) content, as well as the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in mice with liver injury. It could also promote hepatocyte proliferation and inhibit apoptosis by increasing tissue prostaglandin E2 (PGE2) levels. In conclusion, SW033291 demonstrates the capacity to ameliorate APAP-induced hepatic injury in mice by fostering liver regeneration, attenuating oxidative stress, and modulating inflammatory responses, thereby presenting itself as a promising candidate for the development of therapeutic interventions targeting acute liver failure.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151365"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036229","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

Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-20 DOI: 10.1016/j.bbrc.2025.151370

Shinya Sato , Mei Matsukawa , Masaaki Takemoto , Takumi Okamoto , Atsushi Saito , Issei Omura , Koji Matsuhisa , Hiroaki Ikeda , Kazunori Imaizumi , Masayuki Kaneko

Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur. Therefore, to expand the repertoire of ubiquitin ligases that can be utilized in PROTACs, we aimed to develop a versatile system to identify suitable novel ubiquitin ligases for PROTAC-mediated protein degradation using existing PROTACs. Chimeric ubiquitin ligases are constructed by fusing VHL with the ubiquitin ligase of interest that is stably expressed in cells. An existing PROTAC that binds to VHL was added to the cells, and the POI degradation activity was evaluated. In this study, we showed that epidermal growth factor receptor can be degraded by an existing PROTAC utilizing a chimeric ubiquitin ligase that fuses VHL and endoplasmic reticulum-localized ubiquitin ligase, HRD1. These results demonstrate that this novel approach can be used to identify suitable ubiquitin ligases for PROTAC-mediated degradation using existing PROTACs. Expanding the repertoire of ubiquitin ligases that can be utilized for PROTAC by using this versatile system is expected to enable the development of more effective and specific PROTACs for cancer and other diseases.

{"title":"Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs","authors":"Shinya Sato , Mei Matsukawa , Masaaki Takemoto , Takumi Okamoto , Atsushi Saito , Issei Omura , Koji Matsuhisa , Hiroaki Ikeda , Kazunori Imaizumi , Masayuki Kaneko","doi":"10.1016/j.bbrc.2025.151370","DOIUrl":"10.1016/j.bbrc.2025.151370","url":null,"abstract":"<div><div>Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur. Therefore, to expand the repertoire of ubiquitin ligases that can be utilized in PROTACs, we aimed to develop a versatile system to identify suitable novel ubiquitin ligases for PROTAC-mediated protein degradation using existing PROTACs. Chimeric ubiquitin ligases are constructed by fusing VHL with the ubiquitin ligase of interest that is stably expressed in cells. An existing PROTAC that binds to VHL was added to the cells, and the POI degradation activity was evaluated. In this study, we showed that epidermal growth factor receptor can be degraded by an existing PROTAC utilizing a chimeric ubiquitin ligase that fuses VHL and endoplasmic reticulum-localized ubiquitin ligase, HRD1. These results demonstrate that this novel approach can be used to identify suitable ubiquitin ligases for PROTAC-mediated degradation using existing PROTACs. Expanding the repertoire of ubiquitin ligases that can be utilized for PROTAC by using this versatile system is expected to enable the development of more effective and specific PROTACs for cancer and other diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151370"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045477","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, molecular dynamics simulation and antimicrobial activity of novel s-triazine clubbed with three different hybrid pharmacophores

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-19 DOI: 10.1016/j.bbrc.2025.151358

Riki P. Tailor , Krupa G. Prajapati , Mustafa Alhaji Isa , Abidemi Paul Kappo

To address microbial infections and combat drug resistance, we designed, synthesized, and evaluated three novel s-triazine clubbed pharmacophores: 1-acetylpyrazoline (5a-e), 2-aminopyrimidine (6a-e), and 1,5-benzodiazepine (7a-e). These were derived from chalcone (4a-e), showing improved pharmacological profiles. The compounds underwent characterization by FTIR, NMR, and Mass Spectroscopy, and their antimicrobial activities, along with structure-activity relationships (SAR), were assessed using in silico and in vitro methods. Among the tested compounds, 5c, 5e, 6d, 7a, 7d, and 7e demonstrated significant antibacterial activities with MIC values between 50 and 62.5 μg/mL against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa, which indicates their therapeutic potential. Similarly, 5b, 6a, 6c, 7b, and 7c exhibited vigorous antifungal activities against Candida albicans, Aspergillus niger, and Aspergillus clavatus, indicating their broad-spectrum antifungal efficacy. Moreover, the antitubercular potential of the compounds was evaluated against the Mycobacterium tuberculosis H37Rv strain, identifying 5c, 6a, 6d, 7a, and 7d as promising antimycobacterial agents. Molecular docking and molecular dynamics simulation analyses indicated excellent binding energies and stable complexes for 6c, 6e, 7a, and 7e against selected proteins from E. coli, Mycobacterium tuberculosis, and Candida albicans after 40 ns MD simulation. Compound 7a shows the best antimycobacterial activity, while 6c possessed significant antifungal properties in both in silico and in vitro analyses. Moreover, 7a and 7e exhibited desirable antibacterial activities in both experiment, indicating the synthesized compounds' broad-spectrum efficacy against various bacterial and fungal species.

{"title":"Synthesis, molecular dynamics simulation and antimicrobial activity of novel s-triazine clubbed with three different hybrid pharmacophores","authors":"Riki P. Tailor , Krupa G. Prajapati , Mustafa Alhaji Isa , Abidemi Paul Kappo","doi":"10.1016/j.bbrc.2025.151358","DOIUrl":"10.1016/j.bbrc.2025.151358","url":null,"abstract":"<div><div>To address microbial infections and combat drug resistance, we designed, synthesized, and evaluated three novel s-triazine clubbed pharmacophores: 1-acetylpyrazoline (5a-e), 2-aminopyrimidine (6a-e), and 1,5-benzodiazepine (7a-e). These were derived from chalcone (4a-e), showing improved pharmacological profiles. The compounds underwent characterization by FTIR, NMR, and Mass Spectroscopy, and their antimicrobial activities, along with structure-activity relationships (SAR), were assessed using in silico and in vitro methods. Among the tested compounds, 5c, 5e, 6d, 7a, 7d, and 7e demonstrated significant antibacterial activities with MIC values between 50 and 62.5 μg/mL against <em>Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli,</em> and <em>Pseudomonas aeruginosa</em>, which indicates their therapeutic potential. Similarly, 5b, 6a, 6c, 7b, and 7c exhibited vigorous antifungal activities against <em>Candida albicans, Aspergillus niger</em>, and <em>Aspergillus clavatus</em>, indicating their broad-spectrum antifungal efficacy. Moreover, the antitubercular potential of the compounds was evaluated against the <em>Mycobacterium tuberculosis</em> H37Rv strain, identifying 5c, 6a, 6d, 7a, and 7d as promising antimycobacterial agents. Molecular docking and molecular dynamics simulation analyses indicated excellent binding energies and stable complexes for 6c, 6e, 7a, and 7e against selected proteins from <em>E. coli</em>, <em>Mycobacterium tuberculosis</em>, and Candida albicans after 40 ns MD simulation. Compound 7a shows the best antimycobacterial activity, while 6c possessed significant antifungal properties in both in silico and in vitro analyses. Moreover, 7a and 7e exhibited desirable antibacterial activities in both experiment, indicating the synthesized compounds' broad-spectrum efficacy against various bacterial and fungal species.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151358"},"PeriodicalIF":2.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036237","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}

引用次数: 0

Targeted FTO knockout in endothelial cells Boosts adhesion and lowers inflammatory infiltration to alleviate pulmonary arterial hypertension

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-19 DOI: 10.1016/j.bbrc.2025.151339

Ziwen Zhao , Mengmeng Sang , Qi Li , Hao Zhang , Zhiling Luo , Yunhan Zhang , Hanlu Li , Yinbo Ma , Yuanyuan Cheng , Donglin Zhuang , Wenhao Ju , Qiuzhe Guo

Pulmonary arterial hypertension (PAH) is a syndrome characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure, ultimately leading to right heart failure and even death. Increasing evidence implicates the fat mass and obesity-associated protein (FTO) in various metabolic and inflammatory pathways; however, its role in pulmonary endothelial function and PAH remains largely unexplored. In this study, we examined the effects of endothelial cell-specific FTO knockout on PAH development. Our results indicate that the absence of FTO in endothelial cells mitigates hypoxia-induced PAH. Mechanistically, FTO deletion reduces endothelial cell adhesion and inflammatory cell infiltration. Single-cell RNA sequencing revealed disruptions in key inflammatory and adhesion pathways, including TNF-α/NF-κB signaling and VCAM1 expression. These findings suggest that targeting endothelial FTO could be a novel therapeutic strategy for PAH by modulating endothelial adhesion and inflammatory responses.

{"title":"Targeted FTO knockout in endothelial cells Boosts adhesion and lowers inflammatory infiltration to alleviate pulmonary arterial hypertension","authors":"Ziwen Zhao , Mengmeng Sang , Qi Li , Hao Zhang , Zhiling Luo , Yunhan Zhang , Hanlu Li , Yinbo Ma , Yuanyuan Cheng , Donglin Zhuang , Wenhao Ju , Qiuzhe Guo","doi":"10.1016/j.bbrc.2025.151339","DOIUrl":"10.1016/j.bbrc.2025.151339","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a syndrome characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure, ultimately leading to right heart failure and even death. Increasing evidence implicates the fat mass and obesity-associated protein (FTO) in various metabolic and inflammatory pathways; however, its role in pulmonary endothelial function and PAH remains largely unexplored. In this study, we examined the effects of endothelial cell-specific FTO knockout on PAH development. Our results indicate that the absence of FTO in endothelial cells mitigates hypoxia-induced PAH. Mechanistically, FTO deletion reduces endothelial cell adhesion and inflammatory cell infiltration. Single-cell RNA sequencing revealed disruptions in key inflammatory and adhesion pathways, including TNF-α/NF-κB signaling and VCAM1 expression. These findings suggest that targeting endothelial FTO could be a novel therapeutic strategy for PAH by modulating endothelial adhesion and inflammatory responses.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151339"},"PeriodicalIF":2.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051449","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}

引用次数: 0

A novel genetically encoded indicator for deciphering cytosolic and mitochondrial nitric oxide in live cells

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-19 DOI: 10.1016/j.bbrc.2025.151345

Haoqi Li , Zijie Cheng , Huimin Li , Yun Yin , Yuqing Li , Tao Chen , Xin Dong , Qingxun Hu , Dan Wu

Nitric oxide (NO) has been highlighted as a key gaseous signaling molecule in the body, playing a central role in various physiological and pathological processes. However, a comprehensive analysis of NO metabolism dynamics in living cells remains a significant challenge. To address this, we have developed and characterized a novel genetically encoded NO fluorescence sensor, GefiNO, to investigate NO metabolism dynamics in living cells and subcellular organelles. In the study, we described the protein detection capabilities and subcellular spatiotemporal localization of GefiNO sensors. By analyzing NO metabolic responses in macrophages of different subtypes, we provide a comprehensive view of NO dynamics at the cellular level. The GefiNO sensor represents a valuable tool for monitoring extensive NO dynamics in living cells and offers potential for uncovering new insights into cellular metabolic mechanisms.

引用次数: 0

Plasmodium falciparum raf kinase inhibitor is a lipid binding protein that interacts with and regulates the activity of PfCDPK1, an essential plant-like kinase required for red blood cell invasion

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-18 DOI: 10.1016/j.bbrc.2025.151350

Manish Sharma , Deepak Krishnan , Ayushi Singh , Pooja Negi , Komal Rani , Amjesh Revikumar , Manoj Munde , Abhisheka Bansal

Raf Kinase Inhibitor Protein (RKIP) is an important regulator of the MAPK signaling pathway in multicellular eukaryotes. Plasmodium falciparum RKIP (PfRKIP) is a putative phosphatidylethanolamine binding protein (PEBP) that shares limited similarity with Homo sapiens RKIP (HsRKIP). Interestingly, critical components of the MAPK pathway are not expressed in malaria parasites and the physiological function of PfRKIP remains unknown. PfRKIP is expressed throughout the asexual schizogony with maximum expression in late schizonts. Interestingly, PfRKIP and HsRKIP show pH-dependent differential interaction profiles with various lipids. At physiological pH, PfRKIP shows interaction with phosphatidic acid and lipids containing phosphorylated phosphatidylinositol group; however, HsRKIP shows no interaction under the same conditions. Mutation of conserved residues in the PEBP domain of PfRKIP decreases its interaction with PtdIns(3)P. Additionally, in silico docking and mutagenesis studies identified a unique IKK motif within the PEBP domain of PfRKIP that is important for its interaction with the lipids. Using ELISA, we demonstrate the interaction of PfRKIP with PfCDPK1. Importantly, we establish the interaction of PfRKIP and PfCDPK1 within the parasites using immunofluorescence assay and proximity biotinylation technique. Furthermore, our results suggest that PfRKIP regulates the kinase activity of PfCDPK1. In the presence of its substrate, PfCDPK1 hyper-phosphorylates PfRKIP which leads to its dissociation from PfCDPK1. Dissociation of PfRKIP allows PfCDPK1 to trans-phosphorylate its substrates. The molecular mechanism of interaction between PfRKIP and PfCDPK1 may be explored further to identify novel anti-malarial compounds.

{"title":"Plasmodium falciparum raf kinase inhibitor is a lipid binding protein that interacts with and regulates the activity of PfCDPK1, an essential plant-like kinase required for red blood cell invasion","authors":"Manish Sharma , Deepak Krishnan , Ayushi Singh , Pooja Negi , Komal Rani , Amjesh Revikumar , Manoj Munde , Abhisheka Bansal","doi":"10.1016/j.bbrc.2025.151350","DOIUrl":"10.1016/j.bbrc.2025.151350","url":null,"abstract":"<div><div>Raf Kinase Inhibitor Protein (RKIP) is an important regulator of the MAPK signaling pathway in multicellular eukaryotes. <em>Plasmodium falciparum</em> RKIP (PfRKIP) is a putative phosphatidylethanolamine binding protein (PEBP) that shares limited similarity with <em>Homo sapiens</em> RKIP (HsRKIP). Interestingly, critical components of the MAPK pathway are not expressed in malaria parasites and the physiological function of PfRKIP remains unknown. PfRKIP is expressed throughout the asexual schizogony with maximum expression in late schizonts. Interestingly, PfRKIP and HsRKIP show pH-dependent differential interaction profiles with various lipids. At physiological pH, PfRKIP shows interaction with phosphatidic acid and lipids containing phosphorylated phosphatidylinositol group; however, HsRKIP shows no interaction under the same conditions. Mutation of conserved residues in the PEBP domain of PfRKIP decreases its interaction with PtdIns(3)P. Additionally, <em>in silico</em> docking and mutagenesis studies identified a unique IKK motif within the PEBP domain of PfRKIP that is important for its interaction with the lipids. Using ELISA, we demonstrate the interaction of PfRKIP with PfCDPK1. Importantly, we establish the interaction of PfRKIP and PfCDPK1 within the parasites using immunofluorescence assay and proximity biotinylation technique. Furthermore, our results suggest that PfRKIP regulates the kinase activity of PfCDPK1. In the presence of its substrate, PfCDPK1 hyper-phosphorylates PfRKIP which leads to its dissociation from PfCDPK1. Dissociation of PfRKIP allows PfCDPK1 to <em>trans</em>-phosphorylate its substrates. The molecular mechanism of interaction between PfRKIP and PfCDPK1 may be explored further to identify novel anti-malarial compounds.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151350"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021992","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

Inhibition of P2X7 receptor mitigates atrial fibrillation susceptibility in isoproterenol-induced rats

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-18 DOI: 10.1016/j.bbrc.2025.151340

Yunping Zhou , Tianxin Ye , Fangcong Yu , Zhuonan Song , Longbo Wang , Cui Zhang , Bo Yang , Jinxiu Yang , Xingxiang Wang

Background

Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms.

Methods

Two gene expression profiles related to AF (GSE79768 and GSE10598) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. Mendelian randomization (MR) investigated the causal relationship between P2X7R expression and AF. Enrichment analysis was also conducted. An animal model was established via intraperitoneal injection of ISO for 2 weeks. The rats were divided into three groups: control (CTL), ISO, and ISO + Brilliant Blue G (BBG). Cardiac electrophysiological parameters were assessed using programmed electrical stimulation. Myocardial fibrosis and hypertrophy were evaluated using Sirius Red and Wheat Germ Agglutinin staining, respectively. P2X7R abundance was assessed using immunofluorescence, and relevant proteins were detected by Western blotting.

Results

GEO2R and MR analyses indicated a correlation between P2X7R expression and AF. Rats in the ISO group exhibited increased P2X7R levels, abnormal cardiac electrophysiology, altered ion channel protein expression, myocardial hypertrophy, and fibrosis. Enrichment analysis indicated that oxidative stress responses might be involved, and Western blotting showed significantly elevated levels of NOX, CaMKII, and associated proteins. BBG (P2X7R inhibitor) treatment mitigated these effects.

Conclusions

P2X7R was associated with AF, and inhibition of P2X7R curbed electrical and structural remodeling in ISO-induced AF, potentially via the NOX/CaMKII pathway.

{"title":"Inhibition of P2X7 receptor mitigates atrial fibrillation susceptibility in isoproterenol-induced rats","authors":"Yunping Zhou , Tianxin Ye , Fangcong Yu , Zhuonan Song , Longbo Wang , Cui Zhang , Bo Yang , Jinxiu Yang , Xingxiang Wang","doi":"10.1016/j.bbrc.2025.151340","DOIUrl":"10.1016/j.bbrc.2025.151340","url":null,"abstract":"<div><h3>Background</h3><div>Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Two gene expression profiles related to AF (GSE79768 and GSE10598) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. Mendelian randomization (MR) investigated the causal relationship between P2X7R expression and AF. Enrichment analysis was also conducted. An animal model was established via intraperitoneal injection of ISO for 2 weeks. The rats were divided into three groups: control (CTL), ISO, and ISO + Brilliant Blue G (BBG). Cardiac electrophysiological parameters were assessed using programmed electrical stimulation. Myocardial fibrosis and hypertrophy were evaluated using Sirius Red and Wheat Germ Agglutinin staining, respectively. P2X7R abundance was assessed using immunofluorescence, and relevant proteins were detected by Western blotting.</div></div><div><h3>Results</h3><div>GEO2R and MR analyses indicated a correlation between P2X7R expression and AF. Rats in the ISO group exhibited increased P2X7R levels, abnormal cardiac electrophysiology, altered ion channel protein expression, myocardial hypertrophy, and fibrosis. Enrichment analysis indicated that oxidative stress responses might be involved, and Western blotting showed significantly elevated levels of NOX, CaMKII, and associated proteins. BBG (P2X7R inhibitor) treatment mitigated these effects.</div></div><div><h3>Conclusions</h3><div>P2X7R was associated with AF, and inhibition of P2X7R curbed electrical and structural remodeling in ISO-induced AF, potentially via the NOX/CaMKII pathway.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151340"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036213","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

Direct effects of antipsychotics on potassium channels

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-18 DOI: 10.1016/j.bbrc.2025.151344

Wenwen Zhuang, Seo-Yeong Mun, Won Sun Park

Schizophrenia (SCZ) and bipolar disorder (BD) and are severe psychiatric conditions that contribute to disability and increased healthcare costs globally. Although first-, second-, and third-generation antipsychotics are available for treating BD and SCZ, most have various side effects unrelated to their unique functions. Many antipsychotics affect K⁺ channels (Kv, K_Ca, Kir, K_2P, and other channels), which change the functions of various organs. This review summarizes the biological actions of antipsychotics, including off-target side effects involving K⁺ channels.

引用次数: 0

The PDR-type ABC transporter OsPDR1 is involved in leaf senescence by influencing melatonin biosynthesis in rice

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-01-17 DOI: 10.1016/j.bbrc.2025.151355

Junming Zheng, Jinjin Ge, Pengyu Li, Boning Xin, Feng Lin, Wenhua Zhang, Wen Jing

Leaf senescence is a complex developmental process that is regulated by multiple genetic and environmental factors. Understanding the mechanisms underlying the regulation of leaf senescence will provide valuable insights for manipulation of this trait in crops. Here, we report that the ATP-binding cassette (ABC) transporter OsPDR1 is involved in promoting leaf senescence in rice. Mutation and overexpression of OsPDR1 delayed and accelerated natural leaf senescence at the seedling and mature stages, respectively. The level of OsPDR1 transcript in leaves was significantly upregulated by dark treatment. Overexpression of OsPDR1 accelerated dark-induced leaf senescence by enhancing senescence-associated gene expression, whereas its mutation delayed dark-induced leaf senescence. OsPDR1 is coexpressed with the rice N-acetylserotonin methyltransferase gene, OsASMT1, encoding a key enzyme in melatonin biosynthesis. OsASMT1 expression levels and melatonin content were significantly decreased in OsPDR1-overexpressing lines but significantly increased in ospdr1 mutants compared to the wild type. Exogenous melatonin application markedly decreased the accumulation of reactive oxygen species (ROS) and delayed leaf senescence in PDR1.3-overexpressing plants. These results indicated that OsPDR1 plays an important role in the regulation of leaf senescence by influencing melatonin biosynthesis in rice.

{"title":"The PDR-type ABC transporter OsPDR1 is involved in leaf senescence by influencing melatonin biosynthesis in rice","authors":"Junming Zheng, Jinjin Ge, Pengyu Li, Boning Xin, Feng Lin, Wenhua Zhang, Wen Jing","doi":"10.1016/j.bbrc.2025.151355","DOIUrl":"10.1016/j.bbrc.2025.151355","url":null,"abstract":"<div><div>Leaf senescence is a complex developmental process that is regulated by multiple genetic and environmental factors. Understanding the mechanisms underlying the regulation of leaf senescence will provide valuable insights for manipulation of this trait in crops. Here, we report that the ATP-binding cassette (ABC) transporter OsPDR1 is involved in promoting leaf senescence in rice. Mutation and overexpression of <em>OsPDR1</em> delayed and accelerated natural leaf senescence at the seedling and mature stages, respectively. The level of <em>OsPDR1</em> transcript in leaves was significantly upregulated by dark treatment. Overexpression of <em>OsPDR1</em> accelerated dark-induced leaf senescence by enhancing senescence-associated gene expression, whereas its mutation delayed dark-induced leaf senescence. <em>OsPDR1</em> is coexpressed with the rice <em>N</em>-acetylserotonin methyltransferase gene, <em>OsASMT1</em>, encoding a key enzyme in melatonin biosynthesis. <em>OsASMT1</em> expression levels and melatonin content were significantly decreased in <em>OsPDR1</em>-overexpressing lines but significantly increased in <em>ospdr1</em> mutants compared to the wild type. Exogenous melatonin application markedly decreased the accumulation of reactive oxygen species (ROS) and delayed leaf senescence in <em>PDR1.3</em>-overexpressing plants. These results indicated that OsPDR1 plays an important role in the regulation of leaf senescence by influencing melatonin biosynthesis in rice.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151355"},"PeriodicalIF":2.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036244","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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