INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2012
·Vol. 13
·期 5
·5818-5831
·
IF 2.598
Kun Liu,Feng Liu,Nannan Zhang,Shiying Liu,Yuyang Jiang
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.Keywords:Pokemon;anoikis;Bim;hepatoma
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PATHOLOGY
·
2024
·
IF 4.7
Mingxiang Zou,Wenkang Chen,Jing Li,Xin Qi,Xiaobin Wang,Fubing Liu,Jiarui Hu,Qianshi Zhang
This study investigated the role of apoptosis signal-regulated kinase-1 ( ASK1 ) in intervertebral disc degeneration (IDD). The nucleus pulposus (NP) tissues of non-IDD and IDD patients were subjected to hematoxylin and eosin, Safranin O–fast green, and immunohistochemical staining. Quantitative real-time PCR was used to assess the ASK1 mRNA level within NP tissue samples and cells. The Cell Counting Kit-8 assay, senescence-associated β-galactosidase staining, and then flow cytometry were conducted, respectively, to assess the viability, senescence, and apoptosis of NP cells. The extracellular matrix–related factors were detected using Western blot analysis. Furthermore, the effect of ASK1 on the IDD rat model was evaluated through nuclear magnetic resonance imaging analysis, hematoxylin and eosin, Safranin O–fast green staining, and immunohistochemical staining. Finally, c-Jun N-terminal kinase (JNK) inhibitors were used to verify the effect of the JNK/p38 signaling on IDD. ASK1 mRNA and protein were up-regulated within NP tissue samples from the IDD group, IL-1β–stimulated NP cells, and IDD rats. ASK1 inhibition promoted cell viability and repressed the senescence and apoptosis of NP cells; promoted collagen II and aggrecan; inhibited matrix metalloproteinase 3, matrix metalloproteinase 9, a disintegrin and metalloproteinase with thrombospondin motifs 4, and a disintegrin and metalloproteinase with thrombospondin motifs 5 protein levels; and increased NP cells in rat intervertebral disc tissues. ASK1 overexpression exerted the opposite effects of ASK1 inhibition on NP cells. Additionally, JNK/p38 signaling suppression could reverse the ASK1 up-regulation–induced dysfunction. In conclusion, ASK1 facilitated the senescence and apoptosis of NP cells in promoting IDD progression, which may be mediated by the JNK/p38 pathway.
研究领域:
骨科
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2018
·Vol. 392
·期 2
·177-187
·
IF 2.238
Qiao Zhe,Cheng Yao,Liu Shiyuan,Ma Zhenchuan,Li Shaomin,Zhang Wei
Casticin, a flavonoid isolated from Vitex species, has been found to have anti-tumor property in multiple human cancers. The present study aimed to investigate the effect of casticin on the proliferation and apoptosis of esophageal cancer (EC) cells, and further illustrate the underlying mechanisms. In in vitro studies, human EC cell lines TE-1 and ECA-109 were treated with various concentrations of casticin (low-, middle-, and high-dose groups). The results showed that casticin dose-dependently inhibited the proliferation and clonogenicity of EC cells and induced cell cycle arrest in sub-G1 and G2 phases. Furthermore, casticin markedly enhanced EC cell apoptosis as detected by flow cytometry and Hoechst 33342 staining. The level of anti-apoptotic Bcl-2 protein was decreased, while the levels of pro-apoptotic Bax, cleaved-caspase-3, cleaved-caspase-9, and cleaved-PARP were conversely increased in casticin-treated TE-1 and ECA-109 cells. Moreover, casticin decreased the mitochondrial membrane potential and increased the release of mitochondrial cytochrome C into cytoplasm. In addition, the JNK signaling pathway was involved in casticin-medicated anti-proliferation and pro-apoptosis. Cells pretreated with SP600125, a JNK pathway inhibitor, partially abolished the effect of casticin. Finally, the anti-tumor property of casticin was confirmed in in vivo xenograft models. Overall, we provided both in vitro and in vivo evidences that casticin inhibited the proliferation and induced apoptosis of EC cells, and the anti-tumor action of casticin was mediated, in part, by the mitochondrial-dependent apoptosis and the activation of JNK signaling pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Haiyang Zhang,Mian Wei,Xiangyu Lu,Qinghong Sun,Chuqiao Wang,Jiuyan Zhang,Honggang Fan
Aluminum (Al) is an inorganic pollutant that induces nerve cells apoptosis and necroptosis, thereby causing depression and neurodegenerative diseases. IL-1β/JNK signaling pathway can regulate apoptosis and necroptosis. However, it remains unclear whether IL-1β/JNK signaling pathway is involving in the regulation of Al-induced hippocampal neural cells apoptosis and necroptosis. To investigate the mechanism of Al on neural cells apoptosis and necroptosis, rats were orally exposed to different doses of AlCl 3 for 90 days. The open-field test results showed that AlCl 3 caused depressive behavior in rats. Histopathological evidence showed that AlCl 3 induced hippocampal neural cells apoptosis and necrosis. Moreover, Bax/Bcl-2 mRNA expression ratio, caspase-3 activity and mRNA expression and TUNEL positive rates were upregulated, meanwhile, TNF-α mRNA and protein expression levels, TNFR1, RIP1, RIP3 and MLKL proteins levels were increased, while caspase-8 protein level was decreased in the hippocampus of Al-exposed groups. These results proved that AlCl 3 induced hippocampal neural cells apoptosis and necroptosis. Combined with histopathology and correlation analysis, we deduced that hippocampal neural cells were more likely to undergo necroptosis at high doses (450 mg/kg) of AlCl 3 , while <150 mg/kg AlCl 3 tended to induce apoptosis. Finally, AlCl 3 increased the proteins level of IL-1β, IL-1RI, IL-1RAcP, JNK and p-JNK, indicating that AlCl 3 activated IL-1β/JNK signaling pathway. However, the application of IL-1 receptor antagonist (IL-1Ra) inhibited the phosphorylation of JNK and the related genes expression of apoptosis and necroptosis caused by AlCl 3 . Thus, we concluded that AlCl 3 induced hippocampal neural cells death and depression-like behavior in rats by activating IL-1β/JNK signaling pathway.
研究领域:
神经科学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
·
2021
·
IF 2.699
Chuang Zhang,Suolin Li,Chi Sun,Lin Liu,Yanbin Fang,Xiaofeng Yang,Xingxin Pan,Ben Zhang
Objective(s): Vitexin, a natural flavonoid, is commonly found in many foods and traditional herbal medicines and has clear health benefits. However, the role of vitexin in cholestasis is presently unclear. This study investigated whether vitexin mitigated glycochenodeoxycholate (GCDC)-induced hepatocyte injury and further elucidated the underlying mechanisms. Materials and Methods: A cell counting kit-8 (CCK-8) assay was conducted to evaluate cell viability. The mitochondrial membrane potential (MMP, Δψm), reactive oxygen species (ROS) levels, and apoptosis rate of hepatocytes exposed to GCDC were detected by flow cytometry (FCM). We then measured the cytoprotective effects of vitexin against oxidative stress. The molecular signaling pathway was further investigated by using Western blotting and signaling pathway inhibitors. Results: Here, we showed that vitexin increased cell viability and reduced cell apoptosis, necroptosis, and oxidative stress in a dose-dependent manner in GCDC-treated hepatocytes. In addition, by using selective inhibitors, we further confirmed that inhibition of the JAK2/STAT3 pathway by vitexin was mediated by prolonged activation of Sirtuin 6 (SIRT6). Conclusion: Vitexin attenuated GCDC-induced hepatocyte injury via SIRT6 and the JAK2/STAT3 pathways.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Lanqiao Wang,Lanxi Wang,Xu Shi,Shiwen Xu
Excessive chlorpyrifos (CPF) in the environment causes toxicity to nontarget organisms by triggering oxidative stress. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in controlling apoptosis and necrosis by negatively regulating the phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) pathway. However, the effects of different concentrations of CPF on grass fish liver cell injury and the role of the ROS/PTEN/PI3K/AKT axis remain poorly understood. In this study, L8824 cells treated with different concentrations of CPF (0, 40, 60, or 80 μM) were used as the research object. The results showed that the median inhibitory concentration (IC50) was 112.226 μM. As the CPF concentrations increased, the ROS and MDA levels increased, and the T-AOC levels and SOD/GPx/GST activities decreased. As PTEN expression increased, PI3K/AKT, BCL-2, and Caspase-8 expression dramatically decreased. Conversely, RIPK1/RIPK3/MLKL and Bax/Cyt-c/Caspase-3 expression increased. Additionally, necroptosis increased in a dose-dependent manner, while apoptosis first increased and then decreased. In conclusion, our study showed that CPF could trigger oxidative stress and induce apoptosis and necroptosis in fish liver cells by regulating the ROS/PTEN/PI3K/AKT axis, and the type of damage induced was dose-dependent. These results are meaningful for toxicological studies of CPF and efforts to protect the ecosystem.
研究领域:
毒理学
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细胞生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Hangbo Xu,Cao Fang,Changsheng Shao,Lamei Li,Qing Huang
Cold atmospheric plasma (CAP) possesses the ability of high-efficiency disinfection. It is reported that mixtures of reactive oxygen species (ROS) including · OH, 1 O 2 , O 2 − and H 2 O 2 generated from CAP have better antimicrobial ability than mimicked solution of mixture of single ROS type, but the reason is not clear. In this study, CAP was applied to treat yeasts in water in order to investigate the fungal inactivation efficiency and mechanism. The results showed that plasma treatment for 5 min could result in >2-log reduction of yeast cells, and application of varied ROS scavengers could significantly increase the yeast survival rate, indicating that · OH and 1 O 2 played the pivotal role in yeast inactivation. Moreover, the synergistic effect of 1 O 2 with other plasma-generated ROS was revealed. 1 O 2 could diffuse into cells and induce the depolarization of mitochondrial membrane potential (MMP), and different levels of MMP depolarization determined different cell death modes. Mild damage of mitochondria during short-term plasma treatment could lead to apoptosis. For long-term plasma treatment, the cell membrane could be severely damaged by the plasma-generated · OH, so a large amount of 1 O 2 could induce more depolarization of MMP, leading to increase of intracellular O 2 − and Fe 2+ which subsequently caused cell inactivation. 1 O 2 could also induce protein aggregation and increase of RIP1/RIP3 necrosome, leading to necroptosis. With participation of 1 O 2 , endogenous · OH could also be generated via Fenton and Haber-Weiss reactions during plasma treatment, which potentiated necroptosis. Adding l -His could mitigate membrane damage, inhibit the drop of MMP and the formation of necrosome, and thus prevent the happening of necroptosis. These findings may deepen the understanding of plasma sterilization mechanisms and provide guidance for microbial killing in the environment.
研究领域:
环境科学
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微生物学
·
等离子体物理
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产品关联
DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
·
2025
·
IF 2.5
Hou Xiaolu,Hu Guoling,Wang Heling,Yang Ying,Sun Qi,Bai Xiuping
Heart failure (HF) is a clinical syndrome caused by structural or functional abnormalities in heart. Egr2 has been reported to be protective for multiple diseases, but its effect on HF remains unknown. The present study intended to investigate the potential role of Egr2 in HF and its possible downstream effectors. High Egr2 expression in heart was observed in HF mice. Egr2 knockdown alleviated cardiac damage and function in HF mice. Egr2 knockdown inhibited myocardial inflammation and apoptosis both in vivo and in vitro. Egr2 inhibited Acot1 transcription expression via directly binding to its promoter. Acot1 overexpression reduced Lipopolysaccharide (LPS)-induced cardiomyocyte inflammation and apoptosis. Functional rescue experiments revealed that Acot1 reversed the effects of Egr2 on LPS-induced cell apoptosis and inflammation. Overall, Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes by targeting Acot1. This study might provide evidence to better understand the molecular mechanisms of HF pathogenesis. Graphical Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes, possibly through Acot1.
研究领域:
心血管生物学
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分子医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Luyang Liu,Xuanyue Yu,Yuting Huang,Cuiting Liu,Xinyi Xie,Zhongzhen Wu,Jintian Lin,Benshui Shu
Diaphorina citri is a serious citrus pest. Dinotefuran is highly insecticidal against D. citri. To analyze the sublethal effects of dinotefuran on D. citri adults, an indoor toxicity test was performed, which revealed that the lethal concentration 50 (LC50) values were 4.23 and 0.50 μg/mL for 24 and 48 h treatments, respectively. RNA-Seq led to the identification of 71 and 231 differentially expressed genes (DEGs) after dinotefuran treatments with LC20 and LC50 doses, respectively. Many of the DEGs are significantly enriched in the apoptosis pathway. Dinotefuran-induced apoptosis in the gut cells was confirmed through independent assays of 4′,6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Increased levels of reactive oxygen species (ROS) and a loss of mitochondrial membrane potential were observed. Four caspase genes were identified, and dinotefuran treatments resulted in increased mRNA levels of DcCasp1 and DcCasp3a. These findings shed light on the sublethal effects of dinotefuran on D. citri.
研究领域:
昆虫学
·
分子生物学
·
农药科学
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产品关联
DOI
PubMed
高影响因子
BIOFACTORS
·
2021
·Vol. 48
·期 1
·190-203
·
IF 6.113
Huijie Chen,Jianqing Chen,Xu Shi,Lu Li,Shiwen Xu
Bisphenol A (BPA) has caused serious pathologies in varying organs of humans and animals, especially reproductive organs. Naringenin (NRG) is a flavanone compound that has shown protective effects against several environmental chemicals through suppression of oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Herein, we described the discovery path of NRG inhibition on apoptosis in BPA exposed swine testis (ST) cells through targeting Kelch-like ech-associated protein (Keap1). We found that NRG could specifically bound to the active residues of DGR domain in Keap1, thereby activating Nrf2 signaling pathway, and then increasing the levels of SOD, GPx and CAT, and finally inhibiting oxidative stress and mitochondrial apoptosis induced by BPA in ST cells. Altogether, our results showed that NRG inhibits oxidative stress and mitochondrial apoptosis induced by BPA in ST cells by targeting Keap1/Nrf2 signaling pathway, indicating that NRG could serve as an antagonistic therapy against BPA.
研究领域:
毒理学
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生殖生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Zhou Shican,Wu Hang,Ning Wenjuan,Wu Xiao,Xu Xiaoxiao,Ma Yuanqiao,Li Xingwang,Hu Junhong,Wang Chenyu,Wang Junpeng
Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Cuiping Li,Mengfan Pang,Yaping Li,Lirong Han,Yajiao Fan,Xuelian Xin,Xian Zhang,Ning Zhang,Yan Qin
Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol, and stimulates the accumulation of ROS to trigger apoptosis. The preventive effect of vitamin C (Vc) against TCBQ-induced apoptosis in HepG2 cells is unknown. And there is little known about TCBQ-triggered 5-hydromethylcytosine (5hmC)-dependent apoptosis. Here, we confirmed that Vc alleviated TCBQ-induced apoptosis. Through investigating the underlying mechanism, we found TCBQ downregulated 5hmC levels of genomic DNA in a Tet-dependent manner, with a particularly pronounced decrease in the promoter region, using UHPLC-MS-MS analysis and hydroxymethylated DNA immunoprecipitation sequencing. Notably, TCBQ exposure resulted in alterations of 5hmC abundance to ∼91% of key genes at promoters in the mitochondrial apoptosis pathway, along with changes of mRNA expression in 87% of genes. By contrast, 5hmC abundance of genes only exhibited slight changes in the death receptor/ligand pathway. Interestingly, the pretreatment with Vc, a positive stimulator of 5hmC generation, restored 5hmC in the genomic DNA to near-normal levels. More notably, Vc pretreatment further counter-regulated TCBQ-induced alteration of 5hmC abundance in the promoter with 100% of genes, accompanying the reverse modulation of mRNA expressions in 89% of genes. These data from Vc pretreatment supported the relationship between TCBQ-induced apoptosis and the altered 5hmC abundance. Additionally, Vc also suppressed TCBQ-stimulated generation of ROS, and further increased the stability of mitochondria. Our study illuminates a new mechanism of TCBQ-induced 5hmC-dependent apoptosis, and the dual mechanisms of Vc against TCBQ-stimulated apoptosis via reversely regulating 5hmC levels and scavenging ROS. The work also provided a possible strategy for the detoxification of TCBQ.
研究领域:
毒理学
·
分子生物学
·
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
危险品化学品经营许可证（带存储）