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1
المؤلفون: Xudong Wang, Mengqian Zhou, Wenchao Zhang, Hui Wei, Xiaofeng Yao, Beibei Ye, Chao Jing, Yuansheng Duan, Xingchen Li, Shanshan Zhuo, Kai Yue, Yansheng Wu, Dandan Liu, Linqi Li, Qingchuan Lai
المصدر: Theranostics
مصطلحات موضوعية: 0301 basic medicine, Carcinogenesis, Medicine (miscellaneous), medicine.disease_cause, Deubiquitinating enzyme, Mice, 0302 clinical medicine, PSMD14, E2F1, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, Deubiquitinating Enzymes, Prognosis, Pyrrolidinones, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Chemoresistance, medicine.drug, Research Paper, Proteasome Endopeptidase Complex, Mice, Nude, Biology, 03 medical and health sciences, stomatognathic system, Cell Line, Tumor, medicine, otorhinolaryngologic diseases, Animals, Humans, Protein kinase B, neoplasms, PI3K/AKT/mTOR pathway, Cell Proliferation, Squamous Cell Carcinoma of Head and Neck, SOXB1 Transcription Factors, Ubiquitination, Head and neck squamous cell carcinoma, medicine.disease, Thiolutin, Head and neck squamous-cell carcinoma, stomatognathic diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Trans-Activators, Chromatin immunoprecipitation, Proto-Oncogene Proteins c-akt, E2F1 Transcription Factor
الوصف: Increasing evidence reveals a close relationship between deubiquitinating enzymes (DUBs) and cancer progression. In this study, we attempted to identify the roles and mechanisms of critical DUBs in head and neck squamous cell carcinoma (HNSCC). Methods: Bioinformatics analysis was performed to screen differentially expressed novel DUBs in HNSCC. Immunohistochemistry assay was used to measure the expression of DUB PSMD14 in HNSCC specimens and adjacent normal tissues. The level of PSMD14 in HNSCC tumorigenesis was investigated using a 4-NQO-induced murine HNSCC model. The function of PSMD14 was determined through loss-of-function assays. Chromatin immunoprecipitation, immunoprecipitation and in vivo ubiquitination assay were conducted to explore the potential mechanism of PSMD14. The anti-tumor activity of PSMD14 inhibitor Thiolutin was assessed by in vitro and in vivo experiments. Results: We identified PSMD14 as one of significantly upregulated DUBs in HNSCC tissues. Aberrant expression of PSMD14 was associated with tumorigenesis and malignant progression of HNSCC and further indicated poor prognosis. The results of in vitro and in vivo experiments demonstrated PSMD14 depletion significantly undermined HNSCC growth, chemoresistance and stemness. Mechanically, PSMD14 inhibited the ubiquitination and degradation of E2F1 to improve the activation of Akt pathway and the transcription of SOX2. Furthermore, PSMD14 inhibitor Thiolutin exhibited a potent anti-tumor effect on HNSCC in vivo and in vitro by impairing DUB activity of PSMD14. Conclusion: Our findings demonstrate the role and mechanism of PSMD14 in HNSCC, and provide a novel and promising target for diagnosis and clinical therapy of HNSCC.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41457b31fc40f3f3f83e381a98fab731Test
http://europepmc.org/articles/PMC7806466Test -
2
المؤلفون: Yufang Ma, Xiance Sun, Guang Yang, Liping Jiang, Xiaofeng Yao, Xiaoxia Shi, Jingyuan Zhang, Xiuyan Han, Zhanchen Dong, Jian Kang, Shanshan Sha, Tianming Qiu
المصدر: Food and Chemical Toxicology. 157:112540
مصطلحات موضوعية: Lysosomal membrane, Blotting, Western, Toxicology, Mass Spectrometry, Permeability, chemistry.chemical_compound, Tubulin, Autophagy, Humans, Adaptor Proteins, Signal Transducing, Fluorocarbons, Membranes, biology, Permease, Chemistry, Membrane Proteins, Hep G2 Cells, General Medicine, Isotype, Cell biology, Perfluorooctane, Sulfonate, biology.protein, Tyrosine, Lysosomes, After treatment, Food Science
الوصف: Perfluorooctane sulfonate (PFOS) is one kind of persistent organic pollutants. In previous study, we found that PFOS induced autophagy-dependent lysosomal membrane permeabilization (LMP) in hepatocytes, and siRNA against lysosomal permease spinster 1 (SPNS1) relieved PFOS-induced LMP. However, whether and how SPNS1 functioned as the link between autophagy and LMP was still not defined. In this study, we constructed a stable cell line expressing high levels of SPNS1. We found that SPNS1 interacted specifically with α-tubulin of tyrosinated isotype by pull-down assay. After treatment with PFOS, the level of tyrosinated α-tubulin was autophagy-dependently decreased. SPNS1-tyrosinated α-tubulin interaction was disrupted subsequently, which led to LMP eventually. We also found that stable high-expression of SPNS1 in hepatocytes accelerated lysosomal acidification, and deteriorated PFOS-induced LMP. This study pointed out that SPNS1-tyrosinated α-tubulin interaction mediated the cross-talk between autophagy and LMP induced by PFOS, shedding new light on the mechanism of PFOS hepatotoxicity.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f79f1d604a3f0dd3a9f9b362cda63600Test
https://doi.org/10.1016/j.fct.2021.112540Test -
3
المؤلفون: Chengyan Geng, Junjie Mei, Xiaofeng Yao, Zhiguo Li, Qiujuan Li, Jun Cao, Liping Jiang
المصدر: International journal of medicinal mushrooms. 21(6)
مصطلحات موضوعية: 0106 biological sciences, Antioxidant, Asia, genetic structures, medicine.medical_treatment, Apoptosis, Pharmacology, Mitochondrion, Polysaccharide, 01 natural sciences, Applied Microbiology and Biotechnology, 010608 biotechnology, Drug Discovery, medicine, Humans, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Reactive oxygen species, biology, Chemistry, Cytochrome c, Basidiomycota, Fungal Polysaccharides, Hep G2 Cells, biology.organism_classification, Mitochondria, Tacrine, biology.protein, Inonotus obliquus, Medicine, Traditional, Reactive Oxygen Species, medicine.drug
الوصف: Tacrine is the first drug licensed for the treatment of Alzheimer disease. Unfortunately, reversible hepatotoxicity limits its clinical use. In our previous study, we found that tacrine induced apoptosis in HepG2 cells by reactive oxygen species (ROS) formation and mitochondria dysfunction. Inonotus obliquus is a mushroom traditionally used as a folk medicine in Asia. In this study, the possible protective effect of polysaccharides from I. obliquus was investigated. The results showed that I. obliquus polysaccharides (IOP) reduced tacrine-induced apoptosis in HepG2 cells. Inhibition of tacrine-induced ROS generation, 8-OHdG formation in mitochondrial DNA, and loss of the mitochondrial transmembrane potential by IOP were also observed. Furthermore, IOP decreased the cytochrome c release and activation of caspase-3 induced by tacrine. These data suggest that IOP could inhibit tacrine-induced apoptosis in HepG2 cells. The protection is mediated by an antioxidant protective mechanism. Consumption of IOP may be a plausible way to prevent tacrine-induced hepatotoxicity.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7aa2be95e17d3fea9a9d0d85c55c3d9fTest
https://pubmed.ncbi.nlm.nih.gov/31679230Test -
4
المؤلفون: Yu Qiao, Jingxuan Yang, Shanshan Sun, Chuanqiang Wu, Yu Wang, Minghui Zhao, Xudong Wang, Xuan Zhou, Mingyang Liu, Min Li, Feng Yu, Lun Zhang, Zhaoqing Li, Chao Zhang, Yu Ren, Lingping Kong, Yuqing Zhang, Chao Jing, Xiaofeng Yao, Yansheng Wu, Wenyu Guo
المصدر: Clinical Cancer Research. 24:2665-2677
مصطلحات موضوعية: STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Antineoplastic Agents, Mice, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Cell Line, Tumor, otorhinolaryngologic diseases, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, RNA, Small Interfering, STAT3, neoplasms, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cisplatin, Cetuximab, biology, Squamous Cell Carcinoma of Head and Neck, Chemistry, Cell Cycle, EZH2, HOTAIR, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Disease Models, Animal, stomatognathic diseases, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, biology.protein, RNA Interference, RNA, Long Noncoding, HOX Transcript Antisense RNA, Signal Transduction, medicine.drug
الوصف: Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays. Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo. Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89eb7b49550e79381c323aa3511cf71fTest
https://doi.org/10.1158/1078-0432.ccr-16-2248Test -
5
المؤلفون: Xiaoming Liu, Guang Yang, Xiaofeng Yao, Qinghua Sun, Liping Jiang, Min Chen, X Gao, Shaopeng Wang, Xiance Sun
المصدر: Human & Experimental Toxicology. 36:1177-1185
مصطلحات موضوعية: 0301 basic medicine, DNA damage, Health, Toxicology and Mutagenesis, Catechols, Gene Expression, Toxicology, medicine.disease_cause, Umbilical vein, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diethylhexyl Phthalate, Malondialdehyde, Human Umbilical Vein Endothelial Cells, medicine, Humans, chemistry.chemical_classification, Reactive oxygen species, Molecular Structure, biology, Superoxide Dismutase, General Medicine, Glutathione, Molecular biology, Comet assay, Checkpoint Kinase 2, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Comet Assay, Fatty Alcohols, Tumor Suppressor Protein p53, Reactive Oxygen Species, Oxidative stress, DNA Damage
الوصف: Mono (2-ethylhexyl) phthalate (MEHP) is the principal metabolite of di (2-etylhexyl) phthalate, which is widely used as a plasticizer, especially in medical devices. MEHP has toxic effects on cardiovascular system. The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of MEHP in human umbilical vein endothelial cells (HUVECs) and the potential mechanism. The comet assay was used to monitor DNA strand breaks. We have shown that 6-gingerol significantly reduced the DNA strand breaks caused by MEHP. MEHP increased the levels of reactive oxygen species and malondialdehyde, decreased the level of glutathione and activity of superoxide dismutase, and altered the mitochondrial membrane potential. In addition, DNA damage-associated proteins (p53 and p-Chk2 (T68)) were significantly increased by the treatment of MEHP. Those effects can all be protected by 6-gingerol. The results firmly indicate that 6-gingerol may have a strong protective ability against the DNA damage caused by MEHP in HUVECs, and the mechanism may relate to the antioxidant activity.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6047f202225368d680080ad5e1076c1eTest
https://doi.org/10.1177/0960327116681650Test -
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المؤلفون: Liping Jiang, Chengyan Geng, Ming Sun, Guang Yang, Xiance Sun, Xiaofeng Yao, Yueran Bai, Jing Li, Xiaofang Liu, Cong Zhang, Shaopeng Wang, Bo Wang, Qiujuan Li
المصدر: Journal of agricultural and food chemistry. 66(46)
مصطلحات موضوعية: 0301 basic medicine, animal structures, animal diseases, PINK1, Apoptosis, Cathepsin B, Patulin, 03 medical and health sciences, chemistry.chemical_compound, fluids and secretions, 0302 clinical medicine, Mitophagy, Autophagy, Humans, Membrane potential, biology, Chemistry, Cytochrome c, Cytochromes c, General Chemistry, Hep G2 Cells, Cell biology, Mitochondria, 030104 developmental biology, Liver, 030220 oncology & carcinogenesis, cardiovascular system, biology.protein, General Agricultural and Biological Sciences, Lysosomes, Reactive Oxygen Species
الوصف: Patulin (PAT) is a compound produced by fungi including those of the Aspergillus, Penicillium, and Byssochlamys species. PAT has been linked with negative outcomes in certain microorganisms and animal species, but how it causes hepatotoxicity is poorly understood. In this study, we determined that, by treating HepG2 cells using PAT, these cells could be induced to rapidly undergo autophagy, and this was followed within 12 h of treatment by lysosomal membrane permeabilization (LMP) and cathepsin B release. We were able to block these outcomes if cells were treated with 3-methyladenine (3MA), an inhibitor of autophagy, prior to PAT treatment. Moreover, PAT-induced collapse of mitochondrial membrane potential (ΔΨm) depended both on cathepsin B and autophagy. 3MA was further able to reduce the induction of apoptosis in response to PAT, suggesting that autophagy is a driving mechanism for this apoptotic induction. Inhibiting cathepsin B using CA-074 Me further reduced PAT-induced collapses of ΔΨm, mitochondiral cytochrome c release, and apoptosis. We also found that extended treatment of HepG2 cells using PAT over a period of 24 h led to the impairment of mitophagy such that morphologically swollen mitochondria accumulated within cells, and PINK1 failed to colocalize with LC3. Together these data reveal that PAT treatment can promote the induction of apoptosis in HepG2 cells in a manner dependent upon autophagy that progresses via the lysosomal-mitochondrial axis. This study thereby affords new insights into the mechanisms by which PAT drives hepatotoxicity.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33672e3c40240f215a133919a55b906cTest
https://pubmed.ncbi.nlm.nih.gov/30392375Test -
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المؤلفون: Lei Yang, Liping Jiang, Tianming Qiu, Zhidong Wang, Xiance Sun, Ni Gao, Xiaofeng Yao, Pei Pei, Xiaofang Liu, Guang Yang
المصدر: Journal of cellular physiology. 234(4)
مصطلحات موضوعية: 0301 basic medicine, Blood Glucose, Male, Taurine, medicine.medical_specialty, Physiology, Clinical Biochemistry, Population, Autophagy-Related Proteins, Mechanistic Target of Rapamycin Complex 2, Carbohydrate metabolism, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Arsenic Trioxide, Internal medicine, medicine, Autophagy, Animals, Humans, Phosphorylation, education, Mechanistic target of rapamycin, education.field_of_study, biology, Glycogen, Gluconeogenesis, Cell Biology, Hep G2 Cells, medicine.disease, Mice, Inbred C57BL, PPAR gamma, 030104 developmental biology, Endocrinology, chemistry, Liver, 030220 oncology & carcinogenesis, biology.protein, Hepatocytes, Insulin Resistance, Rosiglitazone, Glycolysis, Proto-Oncogene Proteins c-akt, medicine.drug, Signal Transduction
الوصف: Inorganic arsenic (iAs) is reportedly associated with the increased incidence of type 2 diabetes in the population. Here, we found that iAs exposure significantly decreased the expression of glycolytic genes and glycogen content and increased gluconeogenesis gene levels in C57/BL6J mice. The expression of peroxisome proliferator-activated receptor γ (PPARγ), and mechanistic target of rapamycin complex 2 (mTORC2) were decreased in the livers of iAs-treated mice. Furthermore, in iAs-treated HepG2 cells, we found that PPARγ agonist rosiglitazone (RGS) increased the expression of mTORC2, inhibited autophagy, and improved glucose metabolism. mTORC2 agonist palmitic acid inhibited autophagy and improved glucose metabolism as well as the autophagosome formation inhibitor 3-methyladenine. Taurine, a natural compound, reversed impaired glucose metabolism and decreased expression of PPARγ and mTORC2 induced by iAs in mice liver and HepG2 cells. These data indicated that taurine administration could ameliorate iAs-induced insulin resistance through activating PPARγ-mTORC2 signalling and subsequently inhibiting hepatic autophagy.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::727c901d0de7fca5b6893009439e5d07Test
https://pubmed.ncbi.nlm.nih.gov/30362509Test -
8
المؤلفون: Chengyan Geng, Huiyuan Luo, Qiujuan Li, Zhiguo Li, Dan Mei, Jun Cao, Hong Ge, Liping Jiang, Lian Zhao, Xiaofeng Yao
المصدر: Chemico-biological interactions. 277
مصطلحات موضوعية: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Lung Neoplasms, Biology, Toxicology, Focal adhesion, 03 medical and health sciences, Subcutaneous injection, Mice, 0302 clinical medicine, HMGA2, Downregulation and upregulation, Cell Movement, medicine, Animals, Humans, Neoplasm Invasiveness, Lung, A549 cell, Gene knockdown, HMGA2 Protein, General Medicine, Transfection, Up-Regulation, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, A549 Cells, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Matrix Metalloproteinase 2, Environmental Pollutants, Cadmium
الوصف: Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 μM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice. In A549 cells, HMGA2 knockdown significantly decreased expression of MMP-9, MMP-2 and p-FAK and inhibited the migration and invasion compared to that of only Cd-treated cultures. Overexpression of HMGA2 in HEK-293T cells increased expression of MMP-9, MMP-2 and p-FAK and enhanced the migration and invasion compared with the empty vector transfection group. In conclusion, upregulation of HMGA2 plays an important role in Cd-enhanced migration and invasion. Suppressing HMGA2 expression might have potential values in prevention of Cd-resulted toxicities.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e540273501e1fb6783e1712f15596b0Test
https://pubmed.ncbi.nlm.nih.gov/28830677Test -
9
المؤلفون: Zhaoqing Li, Sinan Wang, Na Ye, Jiabin Dong, Xuan Zhou, Minghui Zhao, Yansheng Wu, Yu Wang, Xudong Wang, Yu Ren, Xin Qu, Qiang Shen, Linhgping Kong, Kailiang Zhang, Yu Qiao, Chao Zhang, Shanshan Sun, Xiaofeng Yao, Wenyu Guo, Rui Jin, Lun Zhang, Haiying Chen, Chao Jing, Jia Zhou
مصطلحات موضوعية: 0301 basic medicine, STAT3 Transcription Factor, Cancer Research, medicine.medical_specialty, Beta-catenin, Cell Survival, Cell, Antineoplastic Agents, Salicylanilides, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, STAT3, beta Catenin, Cell Proliferation, biology, Cell growth, Squamous Cell Carcinoma of Head and Neck, Cell cycle, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Oncology, Apoptosis, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Catenin, Cancer research, biology.protein, Carcinoma, Squamous Cell, Niclosamide, Signal transduction, Signal Transduction
الوصف: Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream miR-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0–G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of miR-21. Loss of function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC. Mol Cancer Ther; 16(4); 578–90. ©2017 AACR.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce55a0ac3093153620dc592d3f16ec7fTest
https://europepmc.org/articles/PMC5380531Test/ -
10
المؤلفون: Xiaofang Liu, Shaopeng Wang, Liping Jiang, Nairong Liu, Yueran Bai, Xiance Sun, Guang Yang, Xiaofeng Yao, Xingyue Zhai, Xueyan Wu
المصدر: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 106
مصطلحات موضوعية: 0301 basic medicine, Cell Survival, Caspase 3, Apoptosis, Mitochondrion, Toxicology, Cathepsin B, Cell Line, 03 medical and health sciences, Diethylhexyl Phthalate, Autophagy, Humans, Cathepsin, Membrane Potential, Mitochondrial, TUNEL assay, biology, Cytochrome c, Cytochromes c, Endothelial Cells, General Medicine, Cell biology, Mitochondria, 030104 developmental biology, biology.protein, Lysosomes, Food Science
الوصف: Mono(2-ethylhexyl) phthalate (MEHP), the active metabolite of di(2-ethylhexyl) phthalate (DEHP), has been known to have adverse effects on the reproductive system, urologic systems, hepatic, developmental toxicities and carcinogenicity. However, the effect of MEHP on cardiovascular toxicity remains unclear. Therefore, we aimed to evaluate the cytotoxic effects of MEHP and the possible molecular mechanism. We found that treatment of EA.hy 926 cells with MEHP induced autophagy at earlier time (6 h) in this study. Lysosomal membrane permeabilization (LMP) occurred, after treatment with MEHP for 12 h, followed by the release of cathepsin B. Autophagy inhibitor 3-methyladenine (3MA) attenuated MEHP-induced LMP and the release of cathepsin B in EA.hy 926 cells. Additionally, MEHP induced collapse of mitochondrial transmembrane potential, which was evidenced by JC-1 staining. Addition of 3MA relieved MEHP-induced apoptosis as assessed by the expression of caspase 3 and TUNEL assay, indicating that MEHP-induced apoptosis was autophagy-dependent. Cathepsin B inhibitor, CA-074 Me, suppressed MEHP-induced the mitochondria release of cytochrome c and apoptosis as well. In summary, our results suggest that MEHP induced autophagy-dependent apoptosis in EA.hy 926 cells through the lysosomal-mitochondrial axis. This study provides new mechanistic insights into MEHP-induced cardiovascular toxicity.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c192c5b41bbb558efbe9d4a304e71760Test
https://pubmed.ncbi.nlm.nih.gov/28579546Test