BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Weimin Lin,Xianyu Wen,Xuexin Li,Lei Chen,Wei Wei,Lifan Zhang,Jie Chen
CeRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, C/EBPα was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of C/EBPα and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of C/EBPα and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ , thereby influencing pre-adipocytes adipogenesis . More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of C/EBPα and FOXO1 to influence AdipoQ , thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis.
研究领域:
分子生物学
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细胞生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Zhang Chen-chun,Li Yuan,Jiang Chang-you,Le Qiu-min,Liu Xing,Ma Lan,Wang Fei-fei
The O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is a critical post-translational modification that couples the external stimuli to intracellular signal transduction networks. However, the critical protein targets of O-GlcNAcylation in oxidative stress-induced apoptosis remain to be elucidated. Here, we show that treatment with H 2 O 2 inhibited O-GlcNAcylation, impaired cell viability, increased the cleaved caspase 3 and accelerated apoptosis of neuroblastoma N2a cells. The O-GlcNAc transferase (OGT) inhibitor OSMI-1 or the O-GlcNAcase (OGA) inhibitor Thiamet-G enhanced or inhibited H 2 O 2 -induced apoptosis, respectively. The total and phosphorylated protein levels, as well as the promoter activities of signal transducer and activator of transcription factor 3 (STAT3) and Forkhead box protein O 1 (FOXO1) were suppressed by OSMI-1. In contrast, overexpressing OGT or treating with Thiamet-G increased the total protein levels of STAT3 and FOXO1. Overexpression of STAT3 or FOXO1 abolished OSMI-1-induced apoptosis. Whereas the anti-apoptotic effect of OGT and Thiamet-G in H 2 O 2 -treated cells was abolished by either downregulating the expression or activity of endogenous STAT3 or FOXO1. These results suggest that STAT3 or FOXO1 are the potential targets of O-GlcNAcylation involved in the H 2 O 2 -induced apoptosis of N2a cells.
研究领域:
细胞生物学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 11
·e23681
·
IF 4.4
Shi-shi Liao,Le-le Zhang,Yi-guo Zhang,Jie Luo,Tulanisa Kadier,Ke Ding,Rong Chen,Qing-tao Meng
Ischemia–reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia–reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 μg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.
研究领域:
药理学
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病理生理学
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分子生物学
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DOI
PubMed
高影响因子
Foods
·
2023
·Vol. 12
·期 13
·2471
·
IF 5.2
Jinjie Li,Yi Li,Xiangying Suo,Jiangtao Li,Da Huang,Guangning Kou
Bayberry is known to be a rich source of natural flavonoids and has been reported to have various health-promoting abilities. However, its function on regulating skeletal muscle fiber type remains unclear. This study examined whether bayberry extract affects skeletal muscle fiber type by promoting fast myofiber formation, as well as the potential molecular mechanism. After eight weeks, the “Biqi” bayberry extract (BBE) groups mice displayed markedly enhanced grip strength and improved metabolic rate compared to the control group mice. BBE also significantly increased myofibers size, LDH activity, MyHC-IIb (fast-twitch mRNA) expression, and the percentage of fast-twitch myofibers, while decreasing SDH activity, MyHC-I (slow-twitch mRNA) expression, and slow-twitch myofibers percentage in the skeletal muscle of the mice. The effect of BBE on regulating skeletal muscle fiber type remodeling is likely attributed to its activation of the Akt-FoxO1 pathway. Our findings indicated that BBE can effectively regulate the expression and proportion of fast-twitch fibers, making it a potential therapy for improving glucose homeostasis of skeletal muscle.Keywords:bayberry extract;skeletal muscle;fast-twitch fibers;myofiber type;FoxO1
研究领域:
药理学
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分子生物学
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运动生理学
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DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
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2021
·Vol. 22
·期 5
·609-621
·
IF 2.837
Zheng Jing,Changyuan Wang,Shijie Wen,Yue Jin,Qiang Meng,Qi Liu,Jingjing Wu,Huijun Sun,Mozhen Liu
Background: Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. Objective: This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. Methods: The Osteoprotegerin (OPG)/Receptor Activator of NF-ΚB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. Result: The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. Conclusion: PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.
研究领域:
医学
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分子生物学
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DOI
高影响因子
Cancer Cell International
·
2020
·Vol. 20
·期 1
·1-15
·
IF 4.175
Guo Caixia,Shi Hongmei,Shang Yuli,Zhang Yafei,Cui Jiajia,Yu Hongtao
Background LncRNAs are key regulators in cancer. The current study explored the role of lncRNA LINC00261 (LINC00261) in lung cancer (LC). Methods Expression of LINC00261 in LC tissues and cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Pearson’s Chi square test and Kaplan–Meier analysis were performed to evaluate the correlations between LINC00261 expression and clinical characteristics, and overall survival time. A549 and SPC-A1 cells were transfected with LINC00261 overexpression plasmid, cell viability, cell number, and apoptosis were detected by CCK-8 assay, colony formation, and flow cytometry. Moreover, wound-healing and transwell assay were performed to detect cell metastasis and invasion. Expressions of proteins related to cell proliferation and metastasis were determined by Western blot. Xenograft was constructed, and tumor size and weight were measured and the effects of LINC00261 overexpression on tumor growth were detected. Bioinformatics analysis, dual-luciferase reporter assay, qRT-PCR, correlation analysis, and functional rescue experiments were conducted on clinical cases and LC cells to explore the molecular mechanism of LINC00261 in LC. Results In LC, LINC00261 expression was down-regulated, and was associated with more advanced TNM stage, metastasis and a shorter survival time. LINC00261 overexpression inhibited the growth and metastasis of LC cells in vitro and tumor growth in vivo. Furthermore, miR-1269a directly interacted with LINC00261 and FOXO1. The expressions of miR-1269a and FOXO1 were dysregulated by LINC00261 in LC. Additionally, miR-1269a promoted the progression of LC through targeting FOXO1. Conclusions Down-regulation of LINC00261 expression has a prognostic value in LC, and overexpression LINC00261 inhibits LC progression via targeting miR-1269a/FOXO1 axis.
研究领域:
癌症生物学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
TOXICON
·
2024
·
IF 2.6
Qian Zhang,Xiuzhi Fei,Yue Li,Hengwei Zhang,Lu Chen,Jianping Ruan,Ning Dong
ABSTRACT Fluoride is a double-edged sword. It was widely used for early caries prevention while excessive intake caused a toxicology effect, affected enamel development, and resulted in dental fluorosis. The study aimed to evaluate the protective effect and mechanism of Epigallocatechin-3-gallate (EGCG) on the apoptosis induced by fluoride in ameloblast-like cells. We observed that NaF triggered apoptotic alterations in cell morphology, excessive NaF arrested cell cycle at the G1, and induced apoptosis by up-regulating Bax and down-regulating Bcl-2. NaF activated the insulin-like growth factor receptor (IGFR), and phosphatidylinositol-3-hydroxylase (p-PI3K), while dose-dependently down-regulating the expression of Forkhead box O1 (FoxO1). EGCG supplements reversed the changes in LS8 morphology, the cell cycle, and apoptosis induced by fluoride. These results indicated that EGCG possesses a protective effect against fluoride toxicity. Furthermore, EGCG suppressed the activation of p-PI3K and the down-regulation of FoxO1 caused by fluoride. Collectively, our findings suggested that EGCG attenuated fluoride-induced apoptosis by inhibiting the PI3K/FoxO1 signaling pathway. EGCG may serve as a new alternative method for dental fluorosis prevention, control, and treatment.
研究领域:
牙科学
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毒理学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
REDOX REPORT
·
2025
·
IF 7.4
Fang Cheng,Minzhu Zhao,Qi Wang,Hongli Xiong,Kai Yu,Chong Chen,Ying Zhu,Yemiao Chen,Jianbo Li
Objectives Doxorubicin (DOX) induces dose-dependent cardiotoxicity, primarily through oxidative stress and metabolic dysregulation. Although NAD+ deficiency has been implicated in cardiovascular pathology, its role in DOX-induced cardiotoxicity (DIC) remains poorly understood. This study investigated NAD+ metabolism dysregulation as a redox-sensitive mechanism in DIC pathogenesis.Methods Human cardiomyocytes (AC16), mouse atrial myocytes (HL-1), and C57BL/6 mice were used to establish the DIC model. The role and mechanism of NAD+ in DIC were investigated using a range of methods.Results Using integrated in vitro and in vivo models, we demonstrated that DOX induces myocardial oxidative damage accompanied by NAD+ depletion. Exogenous NAD+ supplementation mitigated the DOX-induced cardiomyocyte death and redox imbalance. Mechanistically, pharmacological CD38 inhibition with 78C or genetic silencing failed to restore the NAD+ pool, whereas nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) overexpression, combined with nicotinamide mononucleotide (NMN) administration, effectively rescued NAD+ levels and attenuated oxidative stress. Computational and functional analyses identified FOXO1 as a transcriptional repressor of NMNAT3 following DOX exposure.Conclusion This study establishes the dysregulation of the FOXO1-NMNAT3 axis as a key mechanism underlying NAD+ depletion in DIC. Targeting this axis through NAD+ replenishment, particularly by activating NMNAT3, offers a novel redox-based therapeutic strategy against DIC.
研究领域:
心血管病理学
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分子生物学
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药理学
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氧化应激
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代谢调控
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转化医学
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药物毒性
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Bo Yu,Dongna Liu,Hongli Zhang,Di Xie,Wei Nie,Kaiyao Shi,Ping Yang
Left ventricular hypertrophy (LVH) is a pathological characteristic shared by distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and its heart protection effect has been recently reported as well. Thus, the current study attempted to validate the anti-hypertrophy effect of atorvastatin as well as the associated mechanism. Hypertrophic feature was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Then the animals and cells were treated with atorvastatin and the effect on cardiac weight and structure as well as cell viability, surface area, and apoptosis was assessed. The mechanism associated with the anti-hypertrophy effect of atorvastatin was further explored by focusing on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of atorvastatin significantly suppressed TAC-induced heart weight increase and attenuated cardiac structure deteriorations in rats. In in vitro assays, atorvastatin increased cell viability, and reduced cell surface area and apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p level. The key role of AMPK during atorvastatin treatment was further validated by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and Compound C, which blocked the pro-survival and anti-hypertrophy effect of atorvastatin on H9c2 cells. The findings outlined in the current study confirmed the anti-hypertrophy effect of atorvastatin and provided a preliminary explanation on the mechanism associated with the treatment: the protective effect of atorvastatin on myocardium against hypertrophy depended on miR-143-3p inhibition via AMPK and Foxo1 activation.
研究领域:
心脏病学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2025
·
IF 3.9
Yijun Yang,Nengyi Wang,Yuankun Chen,Tianpeng Ma,Minhua Weng,Haifeng Wu,Qiuping Wu,Yiqiang Xie,Chuanwu Zhu,Wenting Li
Nonalcoholic fatty liver disease (NAFLD) has posed a huge threat to public health globally, but there are currently no approved drugs available. Growing evidence has proved the close association between increased Th17 cells and NAFLD progression. Interleukin-4 induced protein 1 (IL4I1), an amino acid oxidase secreted by immune cells, was reported to regulate the Th17 cells, but its exact role in NAFLD progression has not been fully explained yet. We found that IL4I1 was highly expressed in the liver of C57BL/6J mice with NAFLD induced by an 8-weeks western diet. To explore the IL4I1’s effect, mice were injected with AAV8 encoding IL4I1 1 week before western diet administration. The results showed that IL4I1 overexpression inhibited the NAFLD progression, demonstrated by relieved liver damage and lipid accumulation. The underlying mechanism in which IL4I1 acts on NAFLD might be attributed to the inactivated AKT/forkhead box protein O1 (FOXO1) signaling pathway–mediated decrease of Th17 cells in liver tissues. Subsequently, by culturing naive CD4 + T cells isolated from the spleen of mice in Th17 cell-polarizing conditions, we determined that IL4I1 overexpression inhibited Th17 cell differentiation by inactivating the AKT/FOXO1 pathway, whereas its knockdown exhibited opposite effects. Further, the AKT activator SC79 reversed the effect of IL4I1 overexpression on Th17 cell differentiation. Collectively, our study supports that compensatory upregulation of IL4I1 protects against liver damage and lipid accumulation in NAFLD progression, partially by inhibiting the activated AKT/FOXO1 signaling pathway-induced Th17 cell differentiation.
研究领域:
免疫学
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肝病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2018
·Vol. 10
·期 10
·1366
·
IF 4.196
Jie Gao,Xin He,Yuejiao Ma,Xuezhi Zhao,Xiaotao Hou,Erwei Hao,Jiagang Deng,Gang Bai
Chlorogenic acid (CGA), a bioactive component in the human diet, is reported to exert beneficial effects on the regulation of glucose metabolism. This study was designed to investigate the specific target of CGA, and explore its underlying mechanisms. Beneficial effects of CGA in glucose metabolism were confirmed in insulin-treated human hepatocarcinoma HepG2 cells. Protein fishing, via CGA-modified functionalized magnetic microspheres, demonstrated the binding of CGA with protein kinase B (AKT). Immunofluorescence using a CGA molecular probe further demonstrated the co-localization of CGA with AKT. A competitive combination test and hampering of AKT membrane translocation showed that CGA might bind to the pleckstrin homology (PH) domain of AKT. The specific binding did not lead to the membrane translocation to phosphatidylinositol (3,4,5)-trisphosphate (PIP3), but directly activated the phosphorylation of AKT on Ser-473, induced the phosphorylation of the downstream molecules, glycogen synthase kinase 3β (GSK3β) and forkhead box O1 (FOXO1), and improved glucose metabolism. Collectively, our data demonstrate that CGA exerts regulatory effects on glucose metabolism via direct targeting the PH domain of AKT. This study clarifies the mechanism of the potential benefits of nutrients containing CGA in the complementary therapy of glucose metabolism disorders.Keywords:chlorogenic acid;glucose metabolism;protein kinase B (AKT);pleckstrin homology (PH) domain;glycogen synthase kinase 3β (GSK3β);forkhead box O1 (FOXO1)
研究领域:
药理学
·
细胞生物学
·
代谢
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2022
·
IF 4.85
Yao Ding,Qinan Wu
Background Type 2 diabetes mellitus (T2DM) is a global health problem that seriously threatens human health. Vitamin D (VD) has antidiabetic effects. However, the protective mechanism of 1,25-dihydroxyvitamin D3 (1,25D) on T2DM is still unclear. Methods A rat model of T2DM was constructed using a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). Glucose tolerance was assessed by an oral glucose tolerance test (OGTT). Insulin secretion in blood and cell supernatant was determined by ELISA. Cell viability was analysed by CCK-8 assay. The level of ROS was detected by the DCFH-DA fluorescent probe method. The iron level in pancreatic tissues and cells was detected by an iron assay kit. Immunofluorescence staining was used to detect the expression of the pancreatic β cell marker CD49a . Furthermore, the protein expression levels of ferroptosis pathway-related proteins and vitamin D receptor (VDR) were detected by western blot . Downstream VDR targets were screened by proteomic sequencing. Results The DM group had increased glucose levels and decreased insulin secretion, while 1,25D treatment decreased glucose levels and increased insulin secretion. 1,25D also suppressed DM-induced ferroptosis in pancreatic tissues in vivo. In addition, 1,25D significantly enhanced the viability of pancreatic β cells and reduced the levels of ROS and iron. 1,25D significantly upregulated the expression of VDR and the ferroptosis-related pathway protein GPX4 and downregulated the expression of ACSL4. Furthermore, knockdown of VDR reversed the effects of 1,25D on cell viability, ROS and iron levels, and ferroptosis-related protein expression in pancreatic β cells. Proteomic sequencing revealed that FOXO1 was the downstream target gene of VDR. Knockdown of FOXO1 reduced pancreatic β cell death, decreased ROS, iron and ACSL4 levels, and increased GPX4 levels. Conclusion 1,25D/VDR inhibited pancreatic β cell ferroptosis in T2DM by downregulating the expression of FOXO1. This study provides a new theoretical basis for basic research on T2DM and is expected to establish a new idea for the treatment of T2DM.
研究领域:
内分泌学
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分子生物学
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糖尿病研究
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细胞生物学
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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）