Biochemical pharmacology最新文献

Corrigendum to “Resveratrol sensitizes breast cancer to PARP inhibitor, talazoparib through dual inhibition of AKT and autophagy flux” [Biochem. Pharmacol. 199 (2022) 115024] “白藜芦醇通过抑制AKT和自噬通量使乳腺癌对PARP抑制剂talazoparib增敏”[Biochem]的更正。药理学杂志，1999,19 (2022):115024 [j]

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-31 DOI: 10.1016/j.bcp.2025.116995

Ganesh Pai Bellare , Birija Sankar Patro

引用次数: 0

Withdrawal notice to “ATR-mediated phosphorylation of RIPK1 inhibits DNA damage-induced necroptosis” [Biochemical Pharmacology 237 (2025) 116949] 关于“atr介导的RIPK1磷酸化抑制DNA损伤诱导的坏死下垂”的撤销通知[生化药理学237(2025)116949]。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-26 DOI: 10.1016/j.bcp.2025.117001

Shen-nan Shi , Qiuyang Xu , Xiaofei Jiao , Yuanjia Wen , Yijie Wu , Jiahao Liu , Ding Ma , Bingbing Zhao , Qinglei Gao , Yong Fang

引用次数: 0

ALKBH5 reverses romidepsin-mediated anti-multiple myeloma activity via regulation of m6A modification of FOXM1 ALKBH5通过调节FOXM1的m6A修饰逆转罗米地辛介导的抗多发性骨髓瘤活性

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-24 DOI: 10.1016/j.bcp.2025.116998

Yaxin Zhang , Xu Cao , Wenjing Li , Zeyu Cui , Jiwei Mao , Ruosi Yao , Linlin Liu

{"title":"ALKBH5 reverses romidepsin-mediated anti-multiple myeloma activity via regulation of m6A modification of FOXM1","authors":"Yaxin Zhang , Xu Cao , Wenjing Li , Zeyu Cui , Jiwei Mao , Ruosi Yao , Linlin Liu","doi":"10.1016/j.bcp.2025.116998","DOIUrl":"10.1016/j.bcp.2025.116998","url":null,"abstract":"<div><div>Multiple myeloma (MM), a prevalent hematological malignancy, is characterized by the abnormal proliferation and accumulation of plasma cells within the bone marrow. ALKBH5, an RNA demethylase, is implicated in various tumor-related processes, yet its role in myeloma remains insufficiently understood. In this study, we revealed that elevated ALKBH5 expression correlates with poor MM prognosis. Furthermore, romidepsin, a recognized histone deacetylase (HDAC) inhibitor, was found to significantly suppress both the protein levels and enzymatic activity of ALKBH5. Interestingly, while ectopic expression of ALKBH5 did not directly influence cell viability, its overexpression mitigated romidepsin-induced apoptosis. Conversely, ALKBH5 knockout enhanced the apoptotic effects of romidepsin, highlighting a potential synergistic interaction. Our findings also demonstrated that ALKBH5 attenuates romidepsin-mediated DNA damage through γH2AX activation. At the mechanistic level, ALKBH5 overexpression reduced m6A methylation of FOXM1 mRNA, stabilizing the transcript and promoting its translation. In contrast, romidepsin increased m6A methylation, accelerating FOXM1 mRNA decay. Notably, reintroduction of ALKBH5 reversed romidepsin’s impact on FOXM1 expression. Additionally, CRISPR/Cas9-mediated ALKBH5 knockout enhanced the synergistic effects of romidepsin by inducing m6A-dependent FOXM1 mRNA destabilization. Our xenograft model further validated that ALKBH5 counteracts romidepsin-induced anti-MM activity by enhancing FOXM1 protein translation. Collectively, these findings illustrate that romidepsin exerts anti-MM effects by impairing ALKBH5 enzymatic activity and promoting FOXM1 mRNA m6A methylation. Therapeutic strategies combining ALKBH5 knockout with romidepsin may offer promising avenues for improving MM treatment outcomes.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"239 ","pages":"Article 116998"},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138913","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}

引用次数: 0

HDAC6 is involved in diabetic nephropathy by regulating TGFβ/Smads and NF-κB signaling pathways. HDAC6通过调节TGFβ/Smads和NF-κB信号通路参与糖尿病肾病。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-23 DOI: 10.1016/j.bcp.2025.116996

Jialin Li, Jiawen Zhang, Xiaocui Huang, Songzhi Jin, Zhaolong Yu, Zhiping Liu, Suzhen Wu

{"title":"HDAC6 is involved in diabetic nephropathy by regulating TGFβ/Smads and NF-κB signaling pathways.","authors":"Jialin Li, Jiawen Zhang, Xiaocui Huang, Songzhi Jin, Zhaolong Yu, Zhiping Liu, Suzhen Wu","doi":"10.1016/j.bcp.2025.116996","DOIUrl":"https://doi.org/10.1016/j.bcp.2025.116996","url":null,"abstract":"<p><p>Histone deacetylase 6 (HDAC6), a cytoplasmic member of the histone deacetylase family, plays an incompletely understood role in diabetic nephropathy (DN). While the TGF-β/Smads and NF-κB signaling pathways are established mediators of renal fibrosis and inflammation respectively, the potential regulatory effect of HDAC6 on these pathways in DN remains to be elucidated. Notably, Smad7 has been documented as a negative regulator of both TGF-β/Smads and NF-κB signaling pathways. This study utilized high glucose to establish a diabetic cell model and employed a high-fat diet combined with STZ injection to create a diabetic animal model to explore HDAC6's role in DN and its potential mechanism. Our research indicates that HDAC6 is upregulated in DN, and inhibiting HDAC6 activity with ACY1215 or downregulating HDAC6 expression with siRNA can suppress the TGF-β/Smads and NF-κB signaling pathways, thereby reducing renal fibrosis and inflammation. Moreover, further studies have shown that lentivirus-mediated overexpression of HDAC6 results in increased expression of FN and p-Smad2/3, decreased expression of Smad7 compared to their respective controls. ACY1215, an HDAC6 inhibitor, could alleviate DN by suppression of both the TGF-β/Smads and NF-κB signaling pathways. To sum up, this study reveals that HDAC6 is involved in the pathogenesis and progression of DN. Mechanistically, HDAC6 may participate in DN by regulating the TGF-β/Smads and NF-κB signaling pathways through Smad7.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116996"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141328","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}

引用次数: 0

Insufficient BK channel function enhances NF-κB nuclear translocation and promotes IL-6 synthesis in vascular smooth muscle cells induced by AT1-AA AT1-AA诱导的血管平滑肌细胞中，BK通道功能不足增强NF-κB核易位，促进IL-6合成。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-23 DOI: 10.1016/j.bcp.2025.117000

Yang Li , Lingxia Xue , Jiayan Feng , Zhuoxi Wang , Yaolin Long , Weiqian Liu , Suli Zhang , Xiaoyan Zhi , Haihu Hao , Xiaohui Wang , Huirong Liu , Li Wang

{"title":"Insufficient BK channel function enhances NF-κB nuclear translocation and promotes IL-6 synthesis in vascular smooth muscle cells induced by AT1-AA","authors":"Yang Li , Lingxia Xue , Jiayan Feng , Zhuoxi Wang , Yaolin Long , Weiqian Liu , Suli Zhang , Xiaoyan Zhi , Haihu Hao , Xiaohui Wang , Huirong Liu , Li Wang","doi":"10.1016/j.bcp.2025.117000","DOIUrl":"10.1016/j.bcp.2025.117000","url":null,"abstract":"<div><div>The inflammatory phenotype of vascular smooth muscle cells (VSMCs) is an important factor in triggering vascular disease, and interleukin-6 (IL-6) is one of the earliest inflammatory cytokines upregulated in many inflammatory contexts. Angiotensin II-1 receptor autoantibody (AT1-AA) can promote the phenotypic transformation of VSMCs into macrophage-like cells, then synthesize abundant IL-6 to induce vascular inflammation. Previous studies suggested that abnormal BK channel function on the surface of VSMCs played an important role in the synthesis of IL-6, but the mechanism of abnormal BK channel involving in AT1-AA-induced IL-6 synthesis in VSMCs was unclear. In this study, the agonist NS1619 of the BK channel and the inhibitor Paxilline were used to reverse or exacerbate IL-6 synthesis in AT1-AA-induced VSMCs. It is known that NF-κB can enter the nucleus due to increased calcium ion concentration caused by BK channel dysfunction, thereby increasing IL-6 transcription. This study observed that Paxilline pretreatment significantly increased the residence time of AT1-AA-induced NF-κB in the nucleus, while NS1619 pretreatment showed the opposite trend. JSH-23 inhibiting NF-κB nuclear entry reversed the increase in IL-6 expression in VSMCs induced by AT1-AA. This study found that AT1-AA enhanced NF-κB nuclear translocation by inhibiting BK channel function, which in turn promoted IL-6 transcription in VSMCs, increased IL-6 synthesis and induced vascular inflammation. This study revealed the importance of BK channel dysfunction in the process of AT1-AA increasing IL-6 synthesis and promoting vascular inflammation, and provided a new idea for alleviating vascular inflammatory diseases from the perspective of improving potassium channel function.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"239 ","pages":"Article 117000"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141392","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}

引用次数: 0

TCPTP inhibition as a novel therapeutic strategy for esophageal squamous cell carcinoma: discovery and efficacy of COH29 抑制TCPTP作为食管鳞状细胞癌的新治疗策略：COH29的发现和疗效

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-23 DOI: 10.1016/j.bcp.2025.116997

Weiwei Li , Yaqian Shi , Xinhuan Chen , Huizhen Wang , Donghui Wei , Jing Yao , Xin Li , Jing Lu , Xiang Li , Junbiao Chang , Yan Qiao

{"title":"TCPTP inhibition as a novel therapeutic strategy for esophageal squamous cell carcinoma: discovery and efficacy of COH29","authors":"Weiwei Li , Yaqian Shi , Xinhuan Chen , Huizhen Wang , Donghui Wei , Jing Yao , Xin Li , Jing Lu , Xiang Li , Junbiao Chang , Yan Qiao","doi":"10.1016/j.bcp.2025.116997","DOIUrl":"10.1016/j.bcp.2025.116997","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that poses a serious threat to human health and is often associated with poor prognosis. Therefore, it is urgent to explore new therapeutic strategies to improve the survival rate of patients with ESCC. T cell protein tyrosine phosphatase (TCPTP) has been reported as a complicated factor in cancer. In this study, we found that TCPTP was highly expressed in ESCC tissues and suppression of TCPTP can effectively inhibit the proliferation of ESCC cells in vitro and in vivo. To identify potential TCPTP inhibitors, we employed a comprehensive research approach encompassing virtual screening, pull down assay, and cellular thermal shift assay. This led to the discovery of two promising candidates: COH29 and gallocatechin gallate (GCG). Both compounds showed inhibitory effects on ESCC cell proliferation, with COH29 displaying superior efficacy. Further enzyme kinetics assay and molecular dynamics simulations confirmed COH29′s unique ability to bind to both the substrate and allosteric sites of TCPTP, making it a promising lead compound for future inhibitor development. Flow cytometry analysis revealed that COH29 treatment caused cell cycle arrest in the G1 phase in ESCC cells. In vivo studies further validated COH29′s robust growth suppression of ESCC, highlighting its potential as a therapeutic agent.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"239 ","pages":"Article 116997"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131455","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}

引用次数: 0

Nur77 inhibits mitochondrial excessive fragmentation through mutated p53 L194F in T47D breast cancer cells 在T47D乳腺癌细胞中，Nur77通过突变的p53 L194F抑制线粒体过度断裂。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-23 DOI: 10.1016/j.bcp.2025.116999

Xiaohui Chen , Fang Zhang , Huiying Zhou , Fu-Quan Jiang , Ting Deng , Guanghui Wang , Jie Liu , Xinyou Liu , Huaqin Sun , Lijun Cai , Yang Xu

{"title":"Nur77 inhibits mitochondrial excessive fragmentation through mutated p53 L194F in T47D breast cancer cells","authors":"Xiaohui Chen , Fang Zhang , Huiying Zhou , Fu-Quan Jiang , Ting Deng , Guanghui Wang , Jie Liu , Xinyou Liu , Huaqin Sun , Lijun Cai , Yang Xu","doi":"10.1016/j.bcp.2025.116999","DOIUrl":"10.1016/j.bcp.2025.116999","url":null,"abstract":"<div><div>Nur77 is an orphan nuclear receptor for which no endogenous ligand has yet been identified. It has been demonstrated that there is aberrant expression or dysfunction of nur77 in breast cancer (BC), however, its role in different types of breast cancer remains contentious. Despite mounting evidence that Nur77 exerts influence over mitochondrial dynamics, including fission, fusion and mitophagy of mitochondria in diverse systems, the role and mechanism of mitochondrial dynamics regulated by Nur77 in tumor cells remain opaque. In the present study, significant differences in Nur77 levels were observed in various BC cell types, particularly in the Luminal A-type cell lines MCF-7 and T47D. Nur77 was more highly expressed in T47D cells with the p53 L194F mutation and significantly promoted the growth of T47D cells. In T47D cells, the knockout of Nur77 unequivocally disrupted mitochondrial function, inducing excessive mitochondrial fragmentation and inactivating mitophagy. Further mechanistic studies demonstrated that only the mutant p53 L194F protein in T47D regulated p-Drp1-S616 in comparison to the wild-type p53 protein in MCF-7 cells. Nur77 up-regulated p53 L194F expression at the transcriptional level and exerted a stronger effect on the interaction of Drp1 with mutant p53 L194F. These results suggest that the Nur77/p53 L194F/ mitofission axis may be involved in the mitochondrial homeostasis of specific types of BC cells to maintain BC cell growth. The discovery of this axis provides an important experimental basis for the fine classification of Luminal A BC and the identification of new therapeutic targets.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"239 ","pages":"Article 116999"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141393","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}

引用次数: 0

Protein prenylation in islet β-cell function in health and metabolic stress 胰岛β细胞在健康和代谢应激中的功能。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-21 DOI: 10.1016/j.bcp.2025.116994

Anjaneyulu Kowluru

{"title":"Protein prenylation in islet β-cell function in health and metabolic stress","authors":"Anjaneyulu Kowluru","doi":"10.1016/j.bcp.2025.116994","DOIUrl":"10.1016/j.bcp.2025.116994","url":null,"abstract":"<div><div>Protein prenylation has been implicated in a variety of cellular functions, including cytoskeletal remodeling, trafficking and fusion of secretory vesicles with the plasma membrane. It involves incorporation of either a 15-carbon farnesyl or a 20-carbon geranylgeranyl derivative of mevalonic acid into cysteines at the C-terminus of substrate proteins. At least four types of prenyltransferases, namely farnesyl transferase (FTase) and the geranylgeranyl transferases I-III (GGTase-I, II, and III) have been identified in mammalian cells. Published evidence suggests expression of functionally active forms of these prenyltransferases and their candidate substrate proteins in human islets, rodent islets, and clonal β-cells. Pharmacological and molecular biological evidence implicates requisite roles for protein prenylation in glucose-stimulated insulin secretion. Evidence is also emerging to indicate significant defects in protein prenylome in β-cell models of impaired insulin secretion and diabetes. This review will provide a status update on modulatory roles of protein prenylation, enzymes involved in this signaling pathway, their structural composition and regulation in the context of islet β-cell function in normal health. In addition, experimental evidence on the metabolic fate of protein prenylation pathway in the pancreatic β-cell following chronic exposure to diabetogenic stimuli is reviewed herein. Lastly, crucial gaps in our current understanding, and potential opportunities for future research in this area of islet biology are highlighted.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"238 ","pages":"Article 116994"},"PeriodicalIF":5.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131853","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}

引用次数: 0

Corrigendum to “Identification of a novel non-ATP-competitive protein kinase inhibitor of PGK1 from marine nature products” [Biochem. Pharmacol. 183 (2021) 114343] “从海洋自然产物中鉴定一种新的非atp竞争性PGK1蛋白激酶抑制剂”的勘误表[生物化学]。药学。183 (2021)114343 [j]

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-16 DOI: 10.1016/j.bcp.2025.116977

Yuying Wang , Lulu Sun , Guihong Yu , Xin Qi , Aotong Zhang , Zhimin Lu , Dehai Li , Jing Li

引用次数: 0

Metformin exhibits inhibitory effects on ferroptosis and alleviates chondrocyte metabolic imbalance in osteoarthritis models, as well as Erastin-induced ferroptosis, through the modulation of the P53/SLC7A11 pathway 二甲双胍通过调节P53/SLC7A11通路，对骨关节炎模型中的铁下垂表现出抑制作用，缓解骨关节炎模型中软骨细胞代谢失衡，以及erastin诱导的铁下垂。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-05-15 DOI: 10.1016/j.bcp.2025.116978

Fan Jiaxin , Jia Xiang , Cui YongPing , Liu Kainan , Xu Tianjie , Zhang Hui , Si Shiqing , Yanhua Cao , Wang Qian

{"title":"Metformin exhibits inhibitory effects on ferroptosis and alleviates chondrocyte metabolic imbalance in osteoarthritis models, as well as Erastin-induced ferroptosis, through the modulation of the P53/SLC7A11 pathway","authors":"Fan Jiaxin , Jia Xiang , Cui YongPing , Liu Kainan , Xu Tianjie , Zhang Hui , Si Shiqing , Yanhua Cao , Wang Qian","doi":"10.1016/j.bcp.2025.116978","DOIUrl":"10.1016/j.bcp.2025.116978","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent degenerative disease, and metformin, the first-line treatment for type 2 diabetes, has shown potential in slowing the progression of OA, although its mechanism of action is not fully understood. This study aims to explore the role of ferroptosis in OA and evaluate the therapeutic effects and mechanisms of metformin on ferroptosis. We identified gene differences associated with OA through RNA-Seq data analysis and predicted potential targets using network pharmacology and molecular docking techniques. In vivo experimental methods, including histological examination, immunofluorescence, Western blotting, real-time quantitative PCR, biochemical analysis, and ELISA, were used to study the effects of metformin in the modified Hulth method and Erastin-induced OA models. The study found that metformin significantly inhibits chondrocyte ferroptosis by upregulating SLC7A11 and downregulating P53 expression, maintaining the balance of synthesis and catabolism in chondrocytes, and effectively slowing down the degeneration of knee joint cartilage in rats. Overall, this study not only provides further evidence for the anti-OA effects of metformin but also identifies its direct targets in the inhibition of ferroptosis in OA.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"238 ","pages":"Article 116978"},"PeriodicalIF":5.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092321","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}

引用次数: 0