Biochemical pharmacology最新文献

{"title":"Cyanine 5-huwentoxin-IV as a novel imaging probe to detect hNav1.7 channel overexpressed in non-small cell lung cancer","authors":"Romain Baudat ,&nbsp;Jérôme Montnach ,&nbsp;Evelyne Benoit ,&nbsp;Claude Zoukimian ,&nbsp;Cathy Carvalhosa ,&nbsp;Rémy Béroud ,&nbsp;Michel De Waard ,&nbsp;Denis Servent","doi":"10.1016/j.bcp.2025.117203","DOIUrl":"10.1016/j.bcp.2025.117203","url":null,"abstract":"<div><div>Currently, tools for detecting cancer cells belonging to the non-small cell lung cancer (NSCLC) are lacking. As overexpression of human voltage-gated sodium channel subtype 1.7 (hNa_v1.7) channels was identified as a promising marker in NSCLC, we investigated whether huwentoxin-IV (HwTx-IV), known to interact preferentially with this sodium channel subtype at nanomolar concentrations, may serve as a practical tool for detecting NSCLC. To achieve this goal, we coupled HwTx-IV to the cyanine 5 fluorophore and evaluated the potential of cyanine 5-HwTx-IV (Cy5-HwTx-IV) as an imaging agent to improve the detection of this cancer type. Increased messager ribonucleic acid (mRNA) expression levels of hNa_v1.7 were confirmed in the A549 and H460 NSCLC cell lines, but not in the Beas-2B healthy lung cell line. Moreover, electrophysiological recordings validated the presence of functional hNa_v1.7 in the metastatic H460 cell line, the recorded Na⁺ current in this cell line being completely abolished in the presence of nanomolar concentrations of Cy5-HwTx-IV and HwTx-IV. In contrast, functional hNa_v1.7 was not detected in the non-metastatic A549 and healthy lung Beas-2B cell lines. Finally, confocal laser scanning microscopy allowed localisation of hNa_v1.7 at the plasma membranes of cells labelled with Cy5-HwTx-IV. In conclusion, this work establishes Cy5-HwTx-IV as a promising tool for NSCLC imaging, thereby enhancing diagnostic precision for this cancer type.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117203"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting pantothenate kinases in human diseases: Biochemistry and pharmacotherapy","authors":"Xinnan Zhang ,&nbsp;Bo Zhang ,&nbsp;Xinze Li ,&nbsp;Feng Qiu ,&nbsp;Qiang Zhang ,&nbsp;Ning Kang","doi":"10.1016/j.bcp.2025.117207","DOIUrl":"10.1016/j.bcp.2025.117207","url":null,"abstract":"<div><div>Pantothenate kinases (PANKs), which regulate the first and rate-limiting step of coenzyme A (CoA) biosynthesis, have emerged as therapeutic targets for various human diseases. PANKs family consists of PANK1, PANK2, PANK3, and PANK4. We summarized the research progress of the PANK family in the last two decades. Notably, PANKs play critical roles in diverse pathophysiological mechanisms underlying human diseases, including pantothenate kinase-associated neurodegeneration (PKAN), propionic acidemia (PA), lipid metabolic disorders, Parkinson’s disease (PD), glioma, clear cell renal cell carcinoma (ccRCC), and insulin resistance (IR). Nevertheless, the precise relationship between PANKs and human diseases remained ambiguous. Therefore, this review provides a comprehensive summary of the structural properties, molecular mechanisms, and relevant modulators that govern PANK activity. In conclusion, targeting PANKs as regulators of CoA biosynthesis and disease pathogenesis contributes to connecting biochemistry with pharmacotherapy.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117207"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium dysregulation in Alzheimer's disease: unraveling the molecular nexus of neuronal dysfunction and therapeutic opportunities.","authors":"Bharat Chaudhary, Sneha Kumari, Rishika Dhapola, Prajjwal Sharma, Mohit Paidlewar, Balachandar Vellingiri, Bikash Medhi, Dibbanti HariKrishnaReddy","doi":"10.1016/j.bcp.2025.117211","DOIUrl":"10.1016/j.bcp.2025.117211","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by Aβ accumulation and tau hyperphosphorylation. Calcium dysregulation also plays a key role in its progression. As a vital second messenger, calcium ions regulate neuronal communication, memory formation, and learning, particularly in the hippocampus. Their levels are influenced by excitatory signaling, synapse formation, and neurotransmitter release. In AD, Ca²⁺ dyshomeostasis occurs near amyloid plaques, marked by elevated intracellular calcium in neurons, microglia, and astrocytes, along with increased neuronal activity. Calcium dyshomeostasis promotes neurofibrillary tangle formation and amyloid-beta deposition through various molecular and signaling pathways. Elevated intracellular calcium accumulation results in multiple pathologies associated with AD, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis, and excitotoxicity through various calcium signaling pathways such as calcineurin (CAN), calcium homeostasis modulator 2 (CALHM2), Mitogen-Activated Protein Kinase, Extracellular Signal-Regulated Kinase/ cAMP Response Element-Binding Protein (MAP/ERK/CREB), Wnt/β-catenin, Transient Receptor Potential Melastatin 2 (TRPM2), and Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) pathway. It is crucial to find the gap between calcium increase overloads and those associated with the neuropathology of AD. Several drugs target calcium signaling pathways and inhibit the disease progression in preclinical and clinical studies. The article highlights the significance of using therapeutic approaches specifically targeting calcium signalling pathways to enhance cognitive performance and decrease the progression of AD. Targeting calcium signalling holds promise for addressing the multifaceted pathologies of AD that will aid in combating the disease.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"117211"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcitonin gene-related peptide (CGRP): A potential therapeutic target against sepsis and sepsis-associated multiple organ failure","authors":"Harshita Singh ,&nbsp;Manoj Naik ,&nbsp;Manisha Suri ,&nbsp;Mohd Hanifa ,&nbsp;Amteshwar Singh Jaggi ,&nbsp;Anjana Bali","doi":"10.1016/j.bcp.2025.117206","DOIUrl":"10.1016/j.bcp.2025.117206","url":null,"abstract":"<div><div>Sepsis, a leading cause of death in intensive care units, is a systemic reaction to infections that causes significant organ damage and necessitates new treatments. Calcitonin gene-related peptide (CGRP) has been identified as a key target in sepsis experimental research. CGRP, a 37 amino acid neuropeptide found throughout the body, plays a beneficial role in sepsis by reducing inflammatory cytokine release, inhibiting the oxidative stress pathway, and decreasing organ-specific inflammation. Research evidence on knockout mice states that specific receptor deficient mice [CGRP receptor activity-modifying protein (RAMP1) and transient receptor potential vanilloid 1 (TRPV1)] exhibited more pronounced neutrophil aggregation and inflammation compared to wild-type mice, suggesting that a CGRP agonism could be a promising treatment for sepsis. Further, CGRP modulates many specific signaling pathways to protect against sepsis-induced multiple organ damage. The present review includes key aspects of CGRP and in-vitro and in-vivo evidence regarding the prevailing contribution of CGRP neuropeptide in ameliorating sepsis-associated organ dysfunction. This study emphasizes the mechanistic insights into the beneficial effects of CGRP on sepsis-associated organ damage. This current review is the first to compile the effects of CGRP in improving sepsis-induced organ dysfunction and underscores its potential as a therapeutic target for organ-specific damage caused by sepsis.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117206"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel covalent inhibitor alleviates type 2 diabetes mellitus by restraining GSK-3β","authors":"Shanhui Zhang ,&nbsp;Fuhui Zhao ,&nbsp;Changluan Pan ,&nbsp;Yajing Wang ,&nbsp;Zhangxiang Yang ,&nbsp;Jing Yang ,&nbsp;Yunniao Meng ,&nbsp;Shaofang Lv ,&nbsp;Jiayu Huang ,&nbsp;Li Dong ,&nbsp;Lei Li ,&nbsp;Yongxi Dong","doi":"10.1016/j.bcp.2025.117205","DOIUrl":"10.1016/j.bcp.2025.117205","url":null,"abstract":"<div><div>Type 2 diabetes (T2DM), which is characterized by insulin resistance and diminished sensitivity, accounts for more than 90 % of the incidence rate of diabetes. At present, the drugs used to treat T2DM in clinic are restricted due to their poor compliance or serious adverse reactions. The abnormally elevated activity of GSK-3β plays an important regulatory role in the occurrence and development of T2DM. Herein, we report the therapeutic effect of a GSK-3β covalent inhibitor <em>N</em>-(3-(4-benzyl-3,5-dioxo-1,2,4-thiadiazol-2-yl) phenyl) acrylamide (<strong>GL10a</strong>), which was discovered by our group with excellent inhibitory activity and homologous kinase selectivity. Further research had confirmed that <strong>GL10a</strong> could inhibit the activity of GSK-3β, thereby increasing the hepatic glycogen synthesis, restoring glucose homeostasis, regulating insulin signaling pathways, and improving pancreatic β-cell function with consequent increase in insulin secretion. Additionally, our findings revealed that <strong>GL10a</strong> exerted beneficial effects on gut microbiota dysbiosis in T2DM, which may contribute to its therapeutic efficacy and facilitate disease recovery. These comprehensive pharmacological properties positioned <strong>GL10a</strong> as a promising candidate, potentially offering novel therapeutic strategies and clinical options for T2DM management.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117205"},"PeriodicalIF":5.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting AKT to treat liver disease: Opportunities and challenges","authors":"Zeping Wang ,&nbsp;Xinyue Dou ,&nbsp;Qiyuan Shan ,&nbsp;Yan Ning,&nbsp;Jiajun Wang,&nbsp;Tianyang Wang,&nbsp;Tianyang Cheng,&nbsp;Kao Shi,&nbsp;Sunan Li,&nbsp;Xin Han,&nbsp;Gang Cao","doi":"10.1016/j.bcp.2025.117208","DOIUrl":"10.1016/j.bcp.2025.117208","url":null,"abstract":"<div><div>AKT, a serine/threonine kinase, is essential for liver homeostasis and is critically involved in the pathogenesis of a wide spectrum of liver diseases. It regulates multiple downstream signaling pathways Through phosphorylation of downstream substrates, AKT modulates key cellular processes including lipid metabolism, apoptosis, oxidative stress, and inflammation. Persistent liver injury, induced by viral infections, alcohol consumption, or high-fat diets, often triggers maladaptive repair mechanisms that can progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma., Recent studies have highlighted the pivotal role of aberrant AKT activation in various hepatic pathological processes, such as metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease, NAFLD), alcoholic liver disease (ALD), and drug-induced liver injury (DILI). This review systematically explores the molecular mechanisms of AKT signaling in liver disease progression, with a focus on the isoform-specific roles of the AKT isoforms (AKT1, AKT2, AKT3). Furthermore, we discuss emerging therapeutic strategies targeting AKT, including small molecule inhibitors and RNA-based modification technologies, alongside the landscape of ongoing clinical trials. Emphasis is placed on early-stage therapeutic interventions and drug resistance mechanisms as a critical direction for future translational research. Overall, this review provides a comprehensive theoretical framework for understanding the multifaceted regulatory functions of AKT in liver diseases and offers valuable insights for the development of precision-targeted therapies.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117208"},"PeriodicalIF":5.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular PET imaging: Unlocking the secrets of cancer metabolism","authors":"Pankaj Garg ,&nbsp;Gargi Singhal ,&nbsp;David Horne ,&nbsp;Prakash Kulkarni ,&nbsp;Ravi Salgia ,&nbsp;Sharad S. Singhal","doi":"10.1016/j.bcp.2025.117202","DOIUrl":"10.1016/j.bcp.2025.117202","url":null,"abstract":"<div><div>Cancer metabolism is a dynamic and complex field, offering insights into tumor growth, progression, and therapy resistance. Molecular positron emission tomography (PET) imaging has emerged as a pivotal tool for visualizing and quantifying metabolic alterations in cancer, shedding light on processes like glycolysis, amino acid metabolism, lipid synthesis, and hypoxia. This review explores the foundational principles of PET imaging, highlighting key radiotracers such as [¹⁸F]-FDG, glutamine-based tracers, and hypoxia-sensitive agents. Clinical applications, including tumor detection, treatment response monitoring, and prognostic assessments, are discussed in detail. Additionally, the review delves into recent innovations such as novel tracers, AI-driven image analysis, and theranostic approaches, while addressing existing challenges and limitations. By integrating molecular imaging with advances in precision oncology, PET holds the potential of revolutionizing the understanding and management of cancer metabolism. This article underscores the transformative potential of molecular PET imaging in cancer research and its implications for future clinical applications.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117202"},"PeriodicalIF":5.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSPAN7 inhibits pancreatic cancer progression by suppressing DNA double-strand break repair and enhances sensitivity to immunochemotherapy","authors":"Hai Lin ,&nbsp;Jiancong Zhou ,&nbsp;Yaning Li ,&nbsp;Lisi Luo ,&nbsp;Yan Zeng ,&nbsp;Xinyue Liang ,&nbsp;Jiaping Yu ,&nbsp;Chengying Ye ,&nbsp;Pengfei Yang ,&nbsp;Yujing Lin ,&nbsp;Yufang Li ,&nbsp;Linjuan Zeng","doi":"10.1016/j.bcp.2025.117199","DOIUrl":"10.1016/j.bcp.2025.117199","url":null,"abstract":"<div><div>Tetraspanin 7 (TSPAN7) plays a crucial role in cancer progression; however, its correlation with pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study aimed to analyse TSPAN7 expression and prognostic value in PDAC by integrating data from public databases and our PDAC cohort. We evaluated the effect of TSPAN7 on PDAC cell proliferation and apoptosis using cell-based assays and mouse xenograft models. Furthermore, molecular biology techniques, including RNA sequencing and liquid chromatography–tandem mass spectrometry, were used to explore underlying mechanisms. Notably, TSPAN7 was significantly downregulated in PDAC tissues and was identified as a favourable prognostic biomarker for PDAC patients. Meanwhile, TSPAN7 overexpression inhibited PDAC cell proliferation and promoted apoptosis <em>in vitro</em>. In mice, TSPAN7 decelerated tumour growth and promoted CD8 + T cell infiltration, consequently enhancing the efficacy of immunochemotherapy against PDAC. Mechanistically, TSPAN7 inhibited RAD51-associated protein 1-mediated DNA double-strand break repair, activating the cGAS–STING signalling pathway to induce type I interferon production. Overall, TSPAN7 inhibits PDAC cell growth and enhances the anti-tumour immune response, indicating its potential as a promising therapeutic target for PDAC.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"242 ","pages":"Article 117199"},"PeriodicalIF":5.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nodosin alleviates cholestatic liver injury by activation of SIRT1/FXR signaling pathway and inhibition of hepatic inflammation.","authors":"Mingzhu Han, Yang Cheng, Wenli Wang, Shengtao Ye, Lingyi Kong, Yanqiu Zhang, Hao Zhang","doi":"10.1016/j.bcp.2025.117200","DOIUrl":"10.1016/j.bcp.2025.117200","url":null,"abstract":"<p><p>Cholestatic liver injury is characterized by abnormal synthesis and excretion of bile acids, which often deteriorates into liver fibrosis, liver cancer and other diseases. Nodosin (Nod), a natural active compound derived from Chinese herb Isodon serra (Maxim.) Kudo, has been reported with valuable bioactivity for anti-cancer and anti-inflammation. However, the mechanism of Nod on cholestatic liver injury has not yet been explored. This research was to investigate the anti-cholestatic effectiveness of Nod and elucidate underlying mechanisms. CYP7A1-promoter-luciferase reporter assay was employed to screen the potential anti-cholestatic compounds. The anti-cholestatic as well as hepatoprotective effects of Nod were validated in AML12 and HepG2 cells, as well as bile duct ligation (BDL) and MDR2^-/- mice. Cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), RNA-sequencing, co-immunoprecipitation, and immunofluorescence were employed to explore the targeting activation of SIRT1/FXR signaling. The results demonstrated that Nod significantly decreased CYP7A1 gene expression and increased FXR protein, but did not affect Fxr/FXR mRNA expression in vivo and in vitro. Nod alleviated cholestasis by maintaining bile acid homeostasis and inhibiting incipient fibrosis in two cholestatic models. Transcriptomics revealed that Nod activated FXR pathway, while restrained inflammation and fibrosis. Mechanistically, Nod stabilized SIRT1 and promoted the deacetylation and phosphorylation of FXR, which activated FXR downstream signaling. In addition, Nod curbed the NF-κB expression and inflammatory response. These findings demonstrate that Nod alleviates cholestasis by activating SIRT1/FXR signaling and down-regulating the NF-κB signaling. Therefore, Nod might be a hopeful therapeutic medicine for cholestasis.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"117200"},"PeriodicalIF":5.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron supplementation protects against renal ischemia–reperfusion injury by enhancing mitochondrial respiratory complex assembly","authors":"Yuanbo Qi ,&nbsp;Zhigang Wang ,&nbsp;Zhaoqi Zhang ,&nbsp;Yongchuang Yan ,&nbsp;Fumin Cheng ,&nbsp;Yi Feng ,&nbsp;Yangxiao Hou ,&nbsp;Haowei Zhu ,&nbsp;Zhou Li ,&nbsp;Zhipeng Xu ,&nbsp;Xinmiao Feng ,&nbsp;Guiwen Feng ,&nbsp;Wenjun Shang","doi":"10.1016/j.bcp.2025.117197","DOIUrl":"10.1016/j.bcp.2025.117197","url":null,"abstract":"<div><div>Ischemia-reperfusion (IR) injury is a major contributor to delayed graft function in kidney transplantation. However, the role of iron in the pathogenesis of renal IR injury and its impact on graft outcomes remains unclear, and the underlying molecular mechanisms are not fully understood. Here, we demonstrated a positive correlation between elevated iron levels and improved renal allograft outcomes both in adult and children kidney transplant patients. Notably, iron sucrose administration, either two weeks or as a single dose injection before surgery, effectively mitigated IR injury in a mouse renal IR injury model. RNA sequencing analysis demonstrated that iron treatment selectively upregulated genes involved in mitochondrial complex assembly and ATP production by inhibiting excessive activation of the PI3K/Akt signaling pathway. Molecular studies further indicated that the improved mitochondrial respiration and reduction in mitochondrial reactive oxygen species (ROS) were primarily mediated by iron-induced facilitation of mitochondrial supercomplex assembly in kidney proximal tubular cells. These findings suggest that intravenous iron administration before transplantation could be a promising therapeutic strategy to improve kidney allograft outcomes.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117197"},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}