JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 9
·e70416
·
IF 4.2
Xiliang Zhu,Qi Liu,Zhaoyun Cheng,Yi Luo
Bisphenol A (BPA) is a widely used industrial chemical with potential endocrine-disrupting effects on metabolic processes. This study investigates the impact of BPA on hepatic function and transcriptional regulation in mouse livers and AML12 cells. Male mice were exposed to low (5 g/kg) and high (50 g/kg) doses of BPA for six weeks. Transcriptomic analysis was performed on liver tissues, and histological examinations were conducted. AML12 cells were treated with varying BPA concentrations, and PPARG transcriptional activity was assessed using a luciferase reporter assay. Additionally, molecular docking, molecular dynamics (MD) simulations, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), MM-PBSA calculations, and multi-species protein structure comparative analysis were employed to analyse the interaction between BPA and PPARG. Transcriptomic analysis revealed a decrease in differentially expressed genes with higher BPA doses, with low-dose exposure significantly downregulating hepatic Cpt1a mRNA levels. Histological examination indicated lipid vacuole formation at high doses without collagen deposition. BPA consistently inhibited PPARG activity in both MCF7 cells and mouse livers. BPA exposure disrupts hepatic lipid metabolism and PPARG activity, highlighting its role as an endocrine disruptor. Further research is needed to elucidate the long-term effects of BPA on liver health.
研究领域:
毒理学
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分子生物学
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代谢研究
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PubMed
高影响因子
Food & Function
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2025
·
IF 5.4
Zhonghua Dong,Xiao Li,Xuan Wang,Jingya Xu,Wei Xu
Background: Diabetic kidney disease (DKD), one of the most common microvascular complications of diabetes mellitus, has been considered the leading cause of end-stage renal disease. Ergosterol is a natural sterol abundant in edible fungi that exhibits pharmacological properties beneficial in the treatment of DKD. However, the precise mechanisms remain elusive. This study aimed to evaluate the therapeutic efficacy of ergosterol in DKD and to delineate the underlying mechanisms. Methods: Transcriptome microarray sequencing data from DKD patients retrieved from the public GEO database, as well as data from mouse DKD models, were analyzed to identify differentially expressed genes. Db/db mouse, high-glucose-induced HK-2 cells and conditioned THP-1 cells were employed to evaluate the impact of ergosterol on renal function, lipid metabolism and macrophage phenotypic transformation. Results: Transcriptional profiling of DKD kidneys revealed alterations in fatty acid metabolism, which were corroborated in db/db mice. Ergosterol significantly improved renal function, reduced lipid accumulation, and mitigated inflammation. CPT1A, a key modulator of fatty acid metabolism, was identified as a target. The inhibition of CPT1A in renal tubular epithelial cells led to impaired fatty acid oxidation and lipid accumulation. Excessive renal lipids further stimulated macrophages to transform into pro-inflammatory phenotypes, leading to renal inflammation infiltration and exacerbating kidney damage. Ergosterol upregulated CPT1A expression through transcriptional regulation of FOXA1, thereby reducing lipid accumulation and subsequent renal inflammation. Conclusion: Ergosterol enhances renal fatty acid oxidation via the FOXA1/CPT1A pathway, reducing renal lipid accumulation and inflammation, potentially delaying DKD progression. This study elucidates the therapeutic potential of ergosterol in DKD and provides new insights into the treatment of DKD.
研究领域:
药理学
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分子生物学
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肾脏病学
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代谢性疾病
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免疫学
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营养科学
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转录组学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Liu Guanjie,Chang Ling,Qian Yihan,Lin Jiacheng,Shang Zhi,Xu Min,Wang Fang,Sun Xuehua,Jiang Yun,Gao Yueqiu,Kong Xiaoni
Non-alcoholic fatty liver disease (NAFLD) is a predominant contributor to end-stage liver disease in the forthcoming decades. Polygonum perfoliatum L. (PPL) is an herbal medicine with anti-lipid peroxidation and anti-inflammatory properties. However, detailed hepatoprotective effects of PPL against NAFLD and its underlying mechanisms are not fully understood. Here, we found that PPL protects against high fat diet (HFD)-induced hepatic steatosis, lipid peroxidation, and glucose-lipid metabolism dysfunction in NAFLD mice. We therefore performed a label-free quantitative proteomic profiling analysis to determine the effect of PPL treatment on liver tissue proteomics and identified that activated PPARs/CPT1A/CPT2-mediated hepatic fatty acid β-oxidation (FAO) process was significantly altered. In vitro treatment of hepatocytes with PPL confirmed this altered process and FAO inhibitor etomoxir (ETO) attenuated the lipid-lowering activity of PPL in hepatocytes. Ultra-high-performance liquid chromatography/Q Exactive-HFX (UPLC/QE-HFX) was used to determine the material basis of anti-NAFLD activity of PPL. Our results have demonstrated the efficacy and potential mechanisms of PPL as an effective pharmacological therapy of NAFLD.
研究领域:
药理学
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肝病学
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蛋白质组学
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代谢学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2024
·
IF 6.1
Meng Wang,Qiurui Li,Shang Wang,Ling Zuo,Yang Hai,Su Yuan,Xuezhi Li,Xuekuan Huang,Congwen Yang,Ling Yao,Wenfu Cao,Guoqing Zuo,Jianwei Wang
Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.
研究领域:
肾病学
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分子生物学
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药理学
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糖尿病研究
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DOI
PubMed
高影响因子
Metabolites
·
2022
·Vol. 12
·期 10
·946
·
IF 5.581
Jing Zhang,Dan Huang,Yue Dai,Yu-Feng Xia
Colitis-associated cancer (CAC), arising from long-lasting intestinal inflammation, is a common type of colorectal cancer. Sinomenine (SIN), the major active compound ofSinomenium acutum, displays excellent antitumor activity. In modern pharmacological research, SIN has been proved to arrest proliferation of human colon cancer cells in vitro, but its functional role and specific mechanism in CAC were still elusive. This study explored the molecular mechanism of SIN on CAC. The results showed that orally administered SIN could decrease the occurrence and development of CAC. Metabolomics results revealed SIN could reprogram metabolism in CAC mice by reversing 34 endogenous metabolites. Importantly, the most prominent metabolic alteration was lipid metabolism. Mechanistically, SIN improved lipid metabolism by enhancing the expression of CPT1A in CAC mice. Moreover, the inhibitory effect of SIN on the proliferation of human colon cancer cells was blunted via CPT1A inhibitor. The results of this study added further evidence of the molecular mechanisms that allow SIN to exert anti-CAC effect by facilitating lipid metabolism and reaffirmed its potential and distinctive role as a chemopreventive agent in CAC.Keywords:sinomenine;colitis-associated cancer;lipid metabolism;UPLC-QTOF-MS/MS;cell proliferation
研究领域:
药理学
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肿瘤学
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代谢组学
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PubMed
高影响因子
Kidney Diseases
·
2023
·Vol. 9
·期 2
·104-117
·
IF 3.7
Xiong Li,He Ting,Liu Chi,Qin Shaozong,Xiao Tangli,Xin Wang,Wang Yaqin,Ran Li,Zhang Bo,Zhao Jinghong
Introduction: Diabetic kidney disease (DKD) is a major source of chronic kidney disease and end-stage renal disease. The injury of glomerulus in DKD is the primary focus; however, proximal tubulopathy also is an indispensable factor in the progression of DKD. Interleukin-37 (IL-37), an anti-inflammatory cytokine of IL-1 family member, has been demonstrated to be associated with diabetes and its relative complications in recent years, but the effect of IL-37 on renal fibrosis in DKD is unclear. Methods: We established streptozotocin plus high fat diet-induced DKD mice model with wild type or IL-37 transgenic mice. Masson and HE staining, immunostaining, and Western blot were used to observe renal fibrosis. In addition, RNA-sequencing was applied to explore the potential mechanisms of IL-37. In vitro, treatment of human proximal tubular (HK-2) cells with 30 mmol/L high glucose or 300 ng/mL recombinant IL-37 further elucidated the possible mechanism of IL-37 inhibition of DKD renal fibrosis. Results: In this work, we first verified the decreased expression of IL-37 in kidney of DKD patient and its correlation with clinical features of renal impairment. Moreover, IL-37 expression markedly attenuated proteinuria and renal fibrosis in DKD mice. Using RNA-sequencing, we found and confirmed a novel role of IL-37 in ameliorating fatty acid oxidation (FAO) reduction of renal tubular epithelial cells both in vivo and in intro. In addition, further mechanistic studies showed that IL-37 alleviated the FAO reduction in HK-2 cells and renal fibrosis in DKD mice through upregulating carnitine palmitoyl-transferase 1A (CPT1A), an important catalyzer for FAO pathway. Conclusion: These data suggest that IL-37 attenuates renal fibrosis via regulating FAO in renal epithelial cells. Upregulation of IL-37 levels might be an effective therapeutic avenue for DKD
研究领域:
肾病学
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内分泌学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Guoqing Zhang,Long Qiu,Kaiyuan Li,Jia Zhao,Xiangnan Li
ESCC samples show higher USP44 succinylation and lower expression vs adjacent non-tumor tissues. • CPT1A binds USP44 and specifically mediates its K543 succinylation, reducing USP44 stability. • K543 succinylation triggers USP44's ubiquitination-mediated degradation in ESCC tissues. • USP44 stabilizes CDK5RAP3 by K166 deubiquitylation, dependent on its catalytic C282 residue. • USP44 inhibits ESCC xenograft growth, lung and lymphatic metastasis by stabilizing CDK5RAP3. Ubiquitin-specific proteases (USPs) function in multiple types of tumor progression by controlling protein turnover. However, the regulatory mechanism of ubiquitin carboxyl-terminal hydrolase 44 (USP44) in esophageal squamous cell carcinoma (ESCC) remains incompletely understood. Here, we show that USP44 expression correlates with tumor size, tumor stage, and TNM stage in ESCC patients. In vitro gain- and loss-of-function experiments validate that USP44 acts as a tumor suppressor in ESCC. Xenograft assays further demonstrate that USP44 overexpression suppresses the growth of ESCC xenografts, as well as lymph node and lung metastasis. Analysis of collected ESCC tumor samples reveals downregulated USP44 expression and upregulated USP44 pan-succinylation, along with two opposing correlations: a negative correlation with Carnitine O-palmitoyltransferase 1 (CPT1A) and a positive correlation with CDK5 regulatory subunit-associated protein 3 (CDK5RAP3). Mechanistic studies identify CPT1A as a lysine succinyltransferase that specifically succinylates USP44 at lysine 543 (K543). Such CPT1A-mediated K543 succinylation triggers ubiquitination-dependent degradation of USP44, thus explaining the downregulation of USP44 observed in clinical ESCC samples. Moreover, ubiquitination proteomics combined with survival analysis identifies CDK5RAP3 as a key deubiquitination substrate of USP44. USP44 directly interacts with CDK5RAP3 and stabilizes CDK5RAP3 by removing its ubiquitin chains at lysine 166 (K166), in a manner dependent on the catalytic cysteine 282 (C282) within its USP domain. In rescue experiments, CDK5RAP3 overexpression reverses the promotion of malignant behavior in ESCC cells and the activation of the Wnt/β-catenin signaling pathway caused by USP44 silencing. Collectively, USP44 may serve as a promising therapeutic target for ESCC.
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高影响因子
Reproductive Biology and Endocrinology
·
2018
·Vol. 16
·期 1
·1-11
·
IF 2.852
Ge Xie,Pan Peng,Jing Jun,Hu Xuechun,Chen Li,Qiu Xuhua,Ma Rujun,Jueraitetibaike Kadiliya,Huang Xuan,Yao Bing
The Sertoli cell is the only somatic cell within the seminiferous tubules, and is vital for testis development and spermatogenesis. Rosiglitazone (RSG) is a member of the thiazolidinedione family and is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. It has been reported that RSG protects various types of cells from fatty acid-induced damage. However, whether RSG serves a protective role in Sertoli cells against palmitic acid (PA)-induced toxicity remains to be elucidated. Therefore, the aim of the present study was to investigate the effect of RSG on PA-induced cytotoxicity in Sertoli cells. MTT assay and Oil Red O staining revealed that RSG ameliorated the PA-induced decrease in TM4 cell viability, which was accompanied by an alleviation of PA-induced lipid accumulation in cells. In primary mouse Sertoli cells, RSG also showed similar protective effects against PA-induced lipotoxicity. Knockdown of PPARγ verified that RSG exerted its protective role in TM4 cells through a PPARγ-dependent pathway. To evaluate the mechanism underlying the protective role of RSG on PA-induced lipotoxicity, the present study analyzed the effects of RSG on PA uptake, and the expression of genes associated with both fatty acid oxidation and triglyceride synthesis. The results demonstrated that although RSG did not affect the endocytosis of PA, it significantly elevated the expression of carnitine palmitoyltransferase (CPT)-1A, a key enzyme involved in fatty acid oxidation, which indicated that the protective effect of RSG may have an important role in fatty acid oxidation. On the other hand, the expression of CPT1B was not affected by RSG. Moreover, the expression levels of diacylglycerol O-acyltransferase (DGAT)-1 and DGAT2, both of which encode enzymes catalyzing the synthesis of triglycerides, were not suppressed by RSG. The results indicated that RSG reduced PA-induced lipid accumulation by promoting fatty acid oxidation mediated by CPT1A. The effect of RSG in protecting cells from lipotoxicity was also found to be specific to Sertoli cells and hepatocytes, and not to other cell types that do not store excess lipid in large quantities, such as human umbilical vein endothelial cells. These findings provide insights into the cytoprotective effects of RSG on Sertoli cells and suggest that PPARγ activation may be a useful therapeutic method for the treatment of Sertoli cell dysfunction caused by dyslipidemia.
研究领域:
药理学
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细胞生物学
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内分泌学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Jian Chen,Zhixiang Wei,Zixuan Song,Sitong Meng,Jiaqi An,Zhenqun Zhang,Yaning Biao,Muqing Zhang,Yixin Zhang
Background Obesity prevalence is rising, increasing risks of metabolic associated fatty liver disease, diabetes mellitus, and cardiovascular disease. Atractylodin (ATR), a bioactive compound from Atractylodes lancea , exhibits potential against metabolic disorders, but its mechanisms against obesity-driven hepatic steatosis remain unclear. Purpose This study aimed to investigate the therapeutic effects and underlying mechanisms of ATR in ameliorating obesity-associated hepatic steatosis via lipid droplet (LD)-mitochondria interactions. Methods Mice were fed a high-fat diet (HFD) for 12 weeks, followed by administration of ATR or Orlistat for 6 weeks beginning at week 6. Hepatic steatosis and molecular targets were assessed via serum biochemistry, histology, fluorescent staining, and Western blot. AML-12 and HepG2 cells were induced with free fatty acids (FFA) and treated with ATR, Atglistatin (ATGLi), etomoxir (ETO), subjected to CPT1A knockdown, or subjected to PLIN2 overexpression/knockdown. In addition to analyzing key proteins and lipid content by molecular and biochemical methods, LD-mitochondria contacts were visualized by transmission electron microscope and laser confocal fluorescence microscopy. Results ATR significantly ameliorated obesity-associated hepatic steatosis in mice and reduced lipid accumulation in AML-12 and HepG2 cells. Visual analysis confirmed that ATR promoted LD-mitochondria contacts. Molecular analysis showed that ATR regulated proteins for lipolysis and fatty acid oxidation (FAO) in liver. Genetic approaches validated that ATR downregulated PLIN2. Mechanistically, ATR promoted LD-mitochondria interactions, lipolysis, and FAO. The effects may be mediated through the regulation of the PLIN2-ATGL/CPT1A axis. Conclusions ATR ameliorates obesity-associated hepatic steatosis by enhancing lipolysis and FAO. Promoting LD-mitochondria interactions represents a promising therapeutic strategy, with ATR showing potential as a therapeutic agent for obesity.
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高影响因子
CHINESE MEDICAL JOURNAL
·
2025
·
IF 7.3
Jia Pengyu,Wang Kui,Cheng Yiqin,Zhang Yan,Lu Yuying,Sun Haodong,Zhang Shuyue,Fan Pei,Zhang Yuanyuan,Yang Liufei,Wang Ning,Lu Haixia,Chen Xinlin,Liu Yong,Wei Haidong,Zhang Pengbo
Plain Language Summary Background: Sevoflurane impairs neurogenesis and cognitive function in the developing brain; however, the underlying mechanisms remain unclear. This study aimed to investigate the role of fatty acid β-oxidation (FAO) in neural stem/progenitor cells (NSPCs) as a potential factor in sevoflurane-induced neurogenesis inhibition and cognitive deficits. Methods: NSPCs, NE-4C cells, and postnatal day 7 (PND 7) rats were exposed to sevoflurane. Cell viability was measured using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Neurogenesis was assessed by immunohistochemistry. Apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Cognitive function was tested with the Morris water maze. Lipid metabolism profiles were analyzed through lipidomics. Message RNA (mRNA) expression levels of key FAO enzymes and the major carnitine transporter were quantified by real-time reverse transcription polymerase chain reaction (RT-qPCR). Protein expression of carnitine palmitoyltransferase 1a (CPT1a) and nuclear peroxisome proliferator-activated receptor α (PPARα) was examined by Western blotting. CPT1a enzymatic activity was determined using a biochemical assay. FAO activity was measured with the FAOBlue assay. Results: Sevoflurane exposure impaired neurogenesis and cognitive function. In NSPCs, sevoflurane exposure induced extensive alterations in lipid metabolism intermediates, inhibited the mRNA expression of acyl-CoA oxidase 1 ( ACOX1 ), acyl-CoA oxidase 3 ( ACOX3 ), hydroxyacyl-CoA dehydrogenase beta subunit ( HADHB ), CPT1a , carnitine palmitoyltransferase 2 ( CPT2 ), acyl-CoA dehydrogenase short-chain ( ACADS ), and solute carrier family 22 member 5 ( SLC22A5 ), suppressed FAO activity, reduced CPT1a expression and activity, and decreased PPARα levels in the nucleus. Enhancing FAO activity in NSPCs ameliorated the negative effects of sevoflurane on neurogenesis. Overexpression of CPT1a rescued the sevoflurane-induced inhibition of FAO activity and neurogenesis in NE-4C cells. Pretreatment with palmitoylethanolamide (PEA), a PPAPα agonist, increased both the nuclear content of PPARα protein and the expression of CPT1a in NSPCs and rat hippocampus after sevoflurane exposure. Furthermore, pretreatment with PEA or the CPT1a substrate carnitine rescued sevoflurane-induced damage to FAO activity in NSPCs, neurogenesis, and cognitive function. Conclusion: Sevoflurane impairs neurogenesis and cognitive function by suppressing FAO in NSPCs of the developing brain. Boosting FAO activity in NSPCs could be a potential strategy to prevent sevoflurane-induced cognitive deficits. Plain Language Summary This study explored how sevoflurane, an anesthetic, affects brain development by impairing neurogenesis and cognitive function. Researchers found that sevoflurane disrupts fatty acid β-oxidation (FAO) in neural stem/progenitor cells (NSPCs), leading to changes in lipid metabolism and reduced expression of key enzymes. Enhancing FAO activity, either by overexpressing certain proteins or using compounds like palmitoylethanolamide (PEA) and carnitine, helped mitigate these negative effects. This suggests that targeting FAO in NSPCs could be a promising approach to counteract sevoflurane-induced cognitive deficits in the developing brain. Text is machine generated and may contain inaccuracies. FAQ
研究领域:
神经科学
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发育生物学
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麻醉学
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代谢学
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干细胞研究
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DOI
高影响因子
Cell Stem Cell
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2025
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IF 20.4
Lei Fan,Qi Tang,Yutong Wang,Hang Sun,Ge Li,Yi Yang,Huiying Zhu,Zhaoyuan Liu,He Wang,Hongyan Wang,Qing Jing,Christopher L. Antos,Hui Xiao,Renchu Guan,Gang Pei,Florent Ginhoux,Zhigang Zhou,An Zeng
Adult hearts scar after injury, while neonatal hearts regenerate. The mechanisms underlying this dichotomy remain unclear. Through comparative spatiotemporal single-cell analyses and dual recombinase-mediated lineage tracing, we uncovered an injury-induced Clusterin + cardiomyocyte ( Clu + CM) population that coordinates reparative, anti-inflammatory macrophage activity. Following injury, Clu + CMs emerge in the border zone of regenerative hearts but are scarce in non-regenerative contexts. These CMs secrete CLU, which binds to macrophage Toll-like receptor 4 (TLR4), attenuating inflammation and promoting reparative polarization through Cpt1a -dependent fatty acid oxidation. These macrophages secrete bone morphogenetic protein 2 (BMP2), activating bone morphogenetic protein receptor, type 1A (BMPR1A) signaling in CMs to drive proliferation. Reduced CLU levels in myocardial infarction patients correlate with impaired cardiac function, whereas Clu overexpression or transplantation of engineered CLU + human cardiac organoids recapitulates this regenerative modulation, enhancing myocardial repair in adult mice. Our findings reveal a critical cardio-immune mechanism whereby Clu + CMs reprogram macrophages to resolve inflammation and stimulate CM proliferation, providing potential strategies for cardiac regeneration.
研究领域:
心脏病学
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免疫学
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再生医学
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分子生物学
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细胞信号传导
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Jingyu Wang,Lin Han,Ziyan Liu,Wei Zhang,Lei Zhang,Jiaru Jing,Ai Gao
Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.
研究领域:
毒理学
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血液学
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分子生物学
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代谢组学
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转录组学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）