المؤلفون: Kai Yue, Yansheng Wu, Beibei Ye, Peng Chen, Qingchuan Lai, Xudong Wang, Chao Jing, Yue Wu, Mengqian Zhou, Yuansheng Duan, Xingchen Li, Xiaofeng Yao, Dandan Liu, Hong Li, Linqi Li, Shengchi Zhang

المصدر: Theranostics

مصطلحات موضوعية: Male, 0301 basic medicine, Esophageal Neoplasms, Carcinogenesis, Medicine (miscellaneous), Snail, medicine.disease_cause, Metastasis, Mice, 0302 clinical medicine, Cell Movement, PSMD14, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, biology, SNAIL, EMT, Esophageal cancer, Pyrrolidinones, Up-Regulation, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Chemosensitivity, Research Paper, medicine.drug, Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Mice, Nude, Antineoplastic Agents, 03 medical and health sciences, Downregulation and upregulation, Esophageal squamous cell carcinoma, In vivo, Cell Line, Tumor, biology.animal, Biomarkers, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Cell Proliferation, Cisplatin, business.industry, Ubiquitination, medicine.disease, Thiolutin, 030104 developmental biology, Trans-Activators, Cancer research, Snail Family Transcription Factors, business

الوصف: Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Methods: Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using in vitro and in vivo experiments. Immunoprecipitation and in vivo ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Results: Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of in vitro and in vivo assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Conclusion: Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c47c33d3831d41492d14a4c177dc6b7Test
https://doi.org/10.7150/thno.46109Test

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

المؤلفون: Rui Jin, Xuan Zhou, Xiaofeng Yao, Qiang Zhang, Ping Li, Chao Jing, Yu Wang, Wenchao Zhang, Yuansheng Duan, Xudong Wang, Yingjie Tao

المصدر: Cancer Letters. 432:38-46

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Adenoid cystic carcinoma, Perineural invasion, Mice, Nude, Motility, Apoptosis, medicine.disease_cause, Metastasis, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Tumor Cells, Cultured, medicine, Animals, Humans, Cell Proliferation, Mice, Inbred BALB C, Mutation, business.industry, Liver Neoplasms, NF-kappa B, Zinc Finger E-box-Binding Homeobox 1, NF-κB, Prognosis, Salivary Gland Neoplasms, medicine.disease, Carcinoma, Adenoid Cystic, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Survival Rate, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, Oncology, chemistry, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, business, Nuclear localization sequence, Signal Transduction

الوصف: Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. In addition, IGFBP2 mutation in the nuclear localization signal could impede nuclear translocation of p65, lower ZEB1 expression, and abrogate the EMT process. In xenograft models, IGFBP2 overexpression promoted lung and liver metastases of SACC cells; while if nuclear IGFBP2 was reduced, the formation of metastases in lung and liver was weakened. Together, these results for the first time demonstrate that IGFBP2 plays an important role in invasion and metastasis of SACC through the NF-κB/ZEB1 signaling pathway and IGFBP2 may be a novel biomarker and target for SACC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d4ac1ce9543ace508a445463d56d618Test
https://doi.org/10.1016/j.canlet.2018.06.008Test

المؤلفون: Tianming Qiu, Xiance Sun, Rushan Yan, Zhidong Wang, Sen Wei, Guang Yang, Ni Gao, Liping Jiang, Xiaofang Liu, Jie Bai, Pei Pei, Shuangyue Qi, Xiaofeng Yao, Lei Yang

المصدر: Cell Death and Disease, Vol 9, Iss 10, Pp 1-16 (2018)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Programmed cell death, Cell Survival, Taurine, Immunology, Inflammation, Real-Time Polymerase Chain Reaction, Arsenic, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Microscopy, Electron, Transmission, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Autophagy, Pyroptosis, medicine, Animals, Humans, Arsenic trioxide, lcsh:QH573-671, Arsenic toxicity, integumentary system, lcsh:Cytology, Inflammasome, Hep G2 Cells, Cell Biology, medicine.disease, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, medicine.symptom, Signal Transduction, medicine.drug

الوصف: Arsenic exposure causes nonalcoholic steatohepatitis (NASH). Inflammation is a key contributor to the pathology of nonalcoholic fatty liver disease (NAFLD), including NASH. However, it is unclear how arsenic induces inflammation. In mouse livers, we show that arsenic trioxide (As2O3) induced NASH, increased autophagy and NLRP3 inflammasome activation, increased lipid accumulation, and resulted in dysregulation of lipid-related genes. Supplemented with taurine (Tau) attenuated the inflammation and autophagy caused by As2O3. In HepG2 cells, we found that As2O3-induced pyroptotic cell death was dependent upon the activation of NLRP3 inflammasome, which was CTSB-dependent. In addition, inhibiting autophagy alleviated the As2O3-induced increase of cytosolic CTSB expression and subsequent release of LDH, activation of the NLRP3 inflammasome, and pyroptosis. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy, CTSB expression, and activation of the NLRP3 inflammasome, and reduced the release of LDH, pyroptotic cell death, and inflammation. Interestingly, As2O3-induced lipid accumulation could not be alleviated by either inhibition of autophagy nor by inhibition of CTSB. Additionally, neither inhibition of the NLRP3 inflammasome or Tau treatment could alleviate lipid accumulation. These results demonstrated that As2O3-induced pyroptosis involves autophagy, CTSB, and the NLRP3 inflammasome cascade, and that Tau alleviates As2O3-induced liver inflammation by inhibiting the autophagic-CTSB-NLRP3 inflammasomal pathway rather than decreasing lipid accumulation. These findings give insight into the association of autophagy, inflammation, pyroptosis, and NASH induced by As2O3.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::35d25f4c13dce5ef8942ce371d4fcc7dTest
http://link.springer.com/article/10.1038/s41419-018-1004-0Test

المؤلفون: Ye Tao, Jinling Wang, Xiance Sun, Xiaofeng Yao, Dan Liu, Zhanchen Dong

المصدر: Mitochondrion. 54

مصطلحات موضوعية: 0301 basic medicine, Bioenergetics, Chemistry, Cell Survival, Cell Biology, Mitochondrion, Extracellular vesicles, DNA, Mitochondrial, Microvesicles, Cell biology, Mitochondria, 03 medical and health sciences, Extracellular Vesicles, 030104 developmental biology, 0302 clinical medicine, Molecular Medicine, Animals, Humans, Viability assay, Energy Metabolism, Molecular Biology, 030217 neurology & neurosurgery, Intracellular, Function (biology)

الوصف: Intercellular transfer of mitochondria and mitochondrial components through extracellular vesicles (EVs), including microvesicles and exosomes, is an area of intense interest. The cargos that are carried by EVs define their biological activities. Mitochondria are in charge of bioenergetics and maintenance of cell viability. Increasing evidences indicate the presence of intact mitochondria or mitochondrial components in EVs, which raises many questions, how they are engulfed into EVs and what do they do? Here, we present what is currently known about the presence and function of various mitochondrial constituent in EVs. We also review current understanding about how and why mitochondrial components are encapsulated into EVs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d05da9f267b48f679c844190e193a038Test
https://pubmed.ncbi.nlm.nih.gov/32861876Test

المؤلفون: Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Liping Jiang, Zeyun Gao, Yong Liu, Xiaoxia Shi, Xuan Wang, Jun Cao, Zhiguo Li

المصدر: Toxicology in vitro : an international journal published in association with BIBRA. 66

مصطلحات موضوعية: 0301 basic medicine, Cell Survival, ATG5, Autophagy-Related Proteins, Toxicology, Autophagy-Related Protein 5, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, Autophagy, Humans, Glycolysis, Lactic Acid, Cell Proliferation, A549 cell, Chemistry, Cell growth, Cell Cycle, General Medicine, Transfection, Cell cycle, Cell biology, Cysteine Endopeptidases, 030104 developmental biology, Glucose, Anaerobic glycolysis, 030220 oncology & carcinogenesis, Cadmium

الوصف: Cadmium (Cd) is a pervasive harmful metal in the environment. It is a well-known inducer of tumorigenesis, but its mechanism is still unclear. We have previously reported that Cd-induced autophagy was apoptosis-dependent and prevents apoptotic cell death to ensure the growth of A549 cells. In this study, the mechanism was further investigated. Cd treatment increased glucose uptake and lactate release significantly. Meanwhile, the protein level of GLUT1，HKII，PKM2 and LDHA increased in a time-dependent manner, indicating that Cd induced aerobic glycolysis in A549 and HELF cells. The inhibitors of autophagy, 3MA, and CQ, repressed Cd-induced glycolysis-related proteins, indicating that autophagy was involved in Cd-induced glycolysis in A549 and HELF cells. Knockdown of ATG4B or ATG5 by siATG4B and siATG5 decreased Cd-induced glycolysis, while overexpression of ATG4B enhanced glycolysis. These results demonstrated that Cd-induced glycolysis was autophagy-dependent. Then, glycolysis inhibitor, 2DG and siPKM2 could inhibit Cd-induced cell viability and cell cycle progression compared to only Cd treatment, indicating that glycolysis played an important role in Cd-induced cell growth. Finally, co-treatment of transfection of ATG4B-DNA plasmids with 2DG or siPKM2 further demonstrated that the autophagy-glycolysis axis played an important role in Cd-induced cell cycle progression. Taken together, our results suggested that Cd-induced glycolysis is autophagy-dependent and the autophagy-glycolysis axis underlies the mechanism of Cd-induced cell growth in A549 and HELF cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbbf1aea4bde2a61bb0478037340cedbTest
https://pubmed.ncbi.nlm.nih.gov/32200033Test

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

المؤلفون: Ming Sun, Cong Zhang, Xiance Sun, Liping Jiang, Xiaofeng Yao, Shaopeng Wang, Xueyan Wu, Guang Yang, Yueran Bai, Xiaofang Liu, Qian Chu

المصدر: Chemico-Biological Interactions. 288:24-31

مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, animal structures, Down-Regulation, Antineoplastic Agents, Apoptosis, Toxicology, Patulin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autophagy, Humans, Viability assay, Cytotoxicity, Membrane Potential, Mitochondrial, Membrane potential, chemistry.chemical_classification, Reactive oxygen species, Chemistry, TOR Serine-Threonine Kinases, Liver Neoplasms, RNA-Binding Proteins, Hep G2 Cells, General Medicine, Acetylcysteine, Up-Regulation, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Toxicity, Reactive Oxygen Species, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt

الوصف: Patulin (PAT) is a secondary metabolite produced by certain species of Penicillium, Byssochlamys and Aspergillus. It has been shown to induce liver toxicity, but the possible molecular mechanisms are not completely elucidated. In our study, we treated Human Hepatoma G2 (HepG2) cells by 3-methyladenine (3-MA), an autophagosome formation inhibitor, and rapamycin, an autophagosome formation stimulator. The results showed that 3-MA protected the HepG2 cells against PAT cytotoxicity, while rapamycin decreased the cell viability. Thus, autophagy may play an important role in PAT-induced toxicity. To uncover the mechanism by which cells decrease proliferation and activation of autophagy, we found that collapses of mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) level were increased under treatment with PAT. Further, we elucidated that the expression of p-Akt1 and p-MTOR was inhibited during this process. N-acetyl-l-cysteine (NAC), a ROS inhibitor, protected against PAT-induced cytotoxicity, decreased the protein expression of LC3-II, and up-regulated the level of p-Akt1 and p-MTOR. These findings suggested that PAT-induced autophagic cell death was ROS-dependent in HepG2 cells. In conclusion, it is possible that PAT elicited autophagy through ROS-Akt1-MTOR pathway in the HepG2 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10e37e3f74769ac0811f1466158d10b9Test
https://doi.org/10.1016/j.cbi.2018.03.018Test

المؤلفون: Xiance Sun, Chengyan Geng, Qiujuan Li, Xiaofang Liu, Xiaofeng Yao, Min Chen, Dandan Li, Guang Yang, Liping Jiang, Chang Feng

المصدر: Chemico-Biological Interactions. 273:212-218

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Population, Peroxisome proliferator-activated receptor, 030204 cardiovascular system & hematology, Biology, Toxicology, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Tumor Cells, Cultured, medicine, Animals, Humans, Oil Red O, PPAR alpha, education, Triglycerides, chemistry.chemical_classification, Mice, Inbred ICR, education.field_of_study, Fenofibrate, Dose-Response Relationship, Drug, Triglyceride, Lipid metabolism, Aurovertins, Hep G2 Cells, General Medicine, Peroxisome, Lipid Metabolism, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Liver, chemistry, Hepatocyte, Hepatocytes, lipids (amino acids, peptides, and proteins), Injections, Intraperitoneal, medicine.drug

الوصف: Citreoviridin (CIT) is a mycotoxin produced by Penicillum citreonigrum, Aspergillus terreus and Eupenicillium ochrosalmoneum. CIT occurs naturally in moldy rice and corn. CIT is associated with the development of atherosclerosis in the general population. Alteration in hepatic lipid metabolism is a pathogenic factor in atherosclerosis. However the effect and the underlying mechanism of CIT on hepatic lipid metabolism are largely unknown. In this study, we reported that CIT induced triglyceride accumulation in mice liver and human liver HepG2 cells as shown in oil red O staining. CIT (0.1 mg/kg-0.3 mg/kg) for 6 weeks elevated liver triglyceride contents in mice. CIT inhibited the transactivation activity of peroxisome proliferator-activated receptor-α (PPAR-α) in hepatocyte in vivo and in vitro, as shown by the reduced mRNA levels of PPAR-α target genes which play key roles in lipid metabolism in various aspects. PPAR-α agonist fenofibrate attenuated CIT-induced triglyceride accumulation in HepG2 cells. Furthermore, CIT increased serum total cholesterol/high-density lipoprotein cholesterol ratio, a strong risk factor for cardiovascular disease. In summary, we reported that CIT induced PPAR-α-dependent hepatic triglyceride accumulation and dyslipidemia. Our data will provide new mechanistic insights into CIT-induced lipid alterations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e173680234d4fddfa3244d0babbf605Test
https://doi.org/10.1016/j.cbi.2017.06.021Test

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