المؤلفون: Ling Yang, Liping Jiang, Xiance Sun, Jing Li, Ningning Wang, Xiaofang Liu, Xiaofeng Yao, Cong Zhang, Haoyuan Deng, Shaopeng Wang, Guang Yang

المصدر: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 164

مصطلحات موضوعية: Male, Diethylhexyl Phthalate, Testis, Ferroptosis, Humans, Testosterone, General Medicine, Tumor Suppressor Protein p53, Toxicology, Reactive Oxygen Species, Lipids, Food Science

الوصف: Exposure to Di (2-ethylhexyl) phthalate (DEHP) has been associated with toxic effects of the reproductive system. However, the exact mechanism remains to be elucidated. In this study we explored the testicular toxicity induced by DEHP, and the probable molecular mechanism in the process. In vivo, the results demonstrated that DEHP affected testosterone levels and blood-testosterone barrier (BTB) integrity and caused ferroptosis. We further demonstrated that DEHP up-regulated the expression of p38α, p-p38α, p53, p-p53, SAT1, ALOX15. This view has also been confirmed in TM4 cells. After pre-treatment with fer-1 or si-MAPK14, the expression of either p53, p-p53, SAT1 and ALOX15 up-regulated by MEHP was inhibited in vitro. Interestingly, p38α can prevent the accumulation of lipid ROS, and the production of lipid ROS in turn promoted the expression of p38α, thus forming a feedback loop during the ferroptosis. In this process, a vicious cycle consisting of p38α, p53, SAT1, ALOX15, lipid ROS was involved. This study provides new mechanistic insights into DEHP-induced toxicity of the reproductive system.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac744e3453214d24768b9c532653c2fdTest
https://pubmed.ncbi.nlm.nih.gov/35447293Test

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

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: 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

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

المؤلفون: Liping Jiang, Xiaona Yan, Linlin Sui, Chengyan Geng, Xiaofeng Yao, Ying Kong, Jun Cao, Huaying Xie, Wei Lv, Qiujuan Li

المصدر: Chemico-biological interactions. 279

مصطلحات موضوعية: 0301 basic medicine, Autophagosome, Autophagy-Related Proteins, Adenocarcinoma, Toxicology, 03 medical and health sciences, Downregulation and upregulation, Western blot, Cell Movement, Cell Line, Tumor, medicine, Autophagy, Humans, Neoplasm Invasiveness, Cell Proliferation, A549 cell, chemistry.chemical_classification, Matrigel, Reactive oxygen species, medicine.diagnostic_test, Chemistry, Cell growth, General Medicine, Cell biology, Up-Regulation, Gene Expression Regulation, Neoplastic, Cysteine Endopeptidases, 030104 developmental biology, Reactive Oxygen Species, Cadmium

الوصف: Cadmium (Cd) is a toxic heavy metal that is widely used in industry and agriculture. In this study the role of autophagy in Cd-induced proliferation, migration and invasion was investigated in A549 cells. Exposure to Cd (2 μM) significantly increased reactive oxygen species (ROS) production, induced autophagy and enhanced cell growth, migration and invasion in A549 cells. Western blot analysis showed that the expression of autophagy-related proteins, LC3-II, Beclin-1 and Atg4 and invasion-related protein MMP-9 were upregulated in Cd-treated cells. N-acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of A549 cells and the increasing protein level of LC3-II and Atg4. Blocking Atg4 expression by siRNA strongly reduced Beclin-1 and LC3-II protein expression and the number of autophagosome positive cells induced by Cd. Furthermore, Atg4 siRNA increased the number of cells at G0/G1 phase, reduced the number of S and G2/M phase cells, and inhibited Cd-induced cell growth significantly compared with that of Cd-treated Control siRNA cells. 3-MA pretreatment increased the percentage of G0/G1 phase cells, decreased S phase and G2/M phase percentage, and inhibited Cd-induced cell growth remarkably compared with that of only Cd-treated cells. Knocking down Atg4 reduced the number of cells that migrated and invaded through the Matrigel matrix significantly and led to a significant decrease of MMP-9 expression. In addition, in lung tissues of Cd-treated BALB/c mice, the increased expression of LC3-II, Beclin-1 and Atg4 were observed. Taken together, our results demonstrated that ROS-dependent Atg4-mediated autophagy plays an important role in Cd-induced cell growth, migration and invasion in A549 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a641bce1ba7be39672e0841ba1d38b8Test
https://pubmed.ncbi.nlm.nih.gov/29179951Test

المؤلفون: Jun Cao, Chengyan Geng, Yue Ding, Xiaofeng Yao, Laifu Zhong, Liping Jiang, Chunpeng Gao

المصدر: Toxicology in Vitro. 28:667-674

مصطلحات موضوعية: Cell Survival, Apoptosis, Mitochondrion, Toxicology, medicine.disease_cause, Cathepsin B, Lysosome, medicine, Humans, Cathepsin, biology, Cytochrome c, Hydrazones, Cytochromes c, Dipeptides, Hep G2 Cells, General Medicine, Mitochondria, Cell biology, medicine.anatomical_structure, Nitroimidazoles, Tacrine, biology.protein, Cholinesterase Inhibitors, Lysosomes, Reactive Oxygen Species, Oxidative stress, medicine.drug

الوصف: Tacrine (THA) is a competitive inhibitor of cholinesterase. Administration of THA for the treatment of Alzheimer’s disease results in a reversible hepatotoxicity in 30–50% of patients, as indicated by elevated alanine aminotransferase levels. However, the intracellular mechanisms have not yet been elucidated. In our previous study, we found that THA induced cytotoxicity and mitochondria dysfunction by ROS generation and 8-OHdG formation in mitochondrial DNA in HepG2 cells. In this study, the mechanism underlying was further investigated. Our results demonstrated that THA induced dose-dependent apoptosis with cytochrome c release and activation of caspase-3. THA-induced apoptosis was inhibited by treating cells with a ROS inhibitor, YCG063. In addition, we observed that THA led to an early lysosomal membrane permeabilization and release of cathepsin B. Pretreatment with CA-074Me, a specific cathepsin B inhibitor resulted in a significant but not complete decrease in tacrine-induced apoptosis. These data suggest that tacrine-induced cell apoptosis involves both mitochondrial damage and lysosomal membrane destabilization, and ROS is the critical factor that integrates tacrine-induced mitochondrial and lysosomal death pathways.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ab2e7bd26ce279f3d17549ea6b0c595Test
https://doi.org/10.1016/j.tiv.2014.02.001Test

المؤلفون: Xiance Sun, Xingyue Zhai, Xiaofeng Yao, Guang Yang, Xueyan Wu, Yueran Bai, Xiaofang Liu, Shaopeng Wang, Liping Jiang, Nairong Liu

المصدر: Toxicology in vitro : an international journal published in association with BIBRA. 44

مصطلحات موضوعية: 0301 basic medicine, Autophagosome, Programmed cell death, Cell Survival, Biology, Toxicology, Cell Line, 03 medical and health sciences, Western blot, Diethylhexyl Phthalate, medicine, Autophagy, Humans, Viability assay, RNA, Small Interfering, Cytotoxicity, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Sirolimus, Reactive oxygen species, medicine.diagnostic_test, Activator (genetics), Adenine, Endothelial Cells, General Medicine, Cell biology, Acetylcysteine, 030104 developmental biology, chemistry, embryonic structures, Reactive Oxygen Species, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt

الوصف: Mono-(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di-(2-ethylhexyl) phthalate (DEHP). MEHP has toxic effects on cardiovascular system, but the possible molecular mechanisms are not completely elucidated. In our study, 3-methyladenine (3-MA), an autophagosome formation inhibitor, protected the EA.hy926 cells against MEHP cytotoxicity, and rapamycin, an autophagosome formation stimulator, further decreased the cell viability in the MEHP-treated EA.hy926 cells. Thus, autophagy may play an important role in MEHP-induced toxicity. MEHP increased the autophagosome number in EA.hy926 cells detected under transmission electron microscope. Collapses of ΔΨm and reactive oxygen species (ROS) level were increased in a dose-dependent manner under treatment with 0-200μM MEHP for 24h. N-acetyl-l-cysteine (NAC), a ROS inhibitor, protected against MEHP-induced cytotoxicity and decreased the protein expression of LC3-II. These findings suggested that MEHP-induced autophagic cell death was ROS-dependent in EA.hy926 cells. Knockdown of Akt1 with Akt1 siRNA aggravated MEHP-induced cell death, and insulin, an Akt1 activator, alleviated MEHP-induced cell death. These results were consistent with the expression of LC3-II using western blot. The phospho-Akt1(Ser473) (p-Akt1) level was enhanced after pretreatment with NAC. In conclusion, it is possible that ROS elicited autophagy through Akt1 pathway in the MEHP-treated EA.hy926 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74131d942e3ff58e01846c3971709d2aTest
https://pubmed.ncbi.nlm.nih.gov/28655635Test

المؤلفون: Xiaofang Liu, Xiaofeng Yao, Guang Yang, Shaopeng Wang, Xiance Sun, Liping Jiang, Qinghua Sun, Min Chen

المصدر: Chemico-biological interactions. 256

مصطلحات موضوعية: 0301 basic medicine, Catechols, Apoptosis, Biology, Ginger, Toxicology, medicine.disease_cause, Protective Agents, 03 medical and health sciences, 0302 clinical medicine, medicine, Autophagy, Human Umbilical Vein Endothelial Cells, Humans, Protein kinase B, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Reactive oxygen species, TOR Serine-Threonine Kinases, Endothelial Cells, General Medicine, Hydrogen Peroxide, Cell biology, Oxidative Stress, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Signal transduction, Fatty Alcohols, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, Oxidative stress, Signal Transduction

الوصف: 6-Gingerol, the major pharmacologically-active component of ginger, has the potential to prevent heart disease. However, the mechanisms are not well understood. In this study, the protective effect of 6-gingerol against hydrogen peroxide-induced apoptosis in human umbilical vein endothelial cells (HUVECs) was investigated. Apoptosis was detected by Hoechst 33342 and Flow cytometry analysis. To further elucidate the crosstalk between apoptosis and autophagy, we tested the expression of autophagy related proteins, LC3B, Bcl-2, Beclin1, AKT, p-AKT, mechanistic target of rapamycin (mTOR), and p-mTOR. Furthermore, mitochondrial membrane potential and the intracellular generation of reactive oxygen species (ROS) were also investigated. Our data revealed that 6-gingerol significantly reduced apoptosis by inducing autophagy. It has been demonstrated that 6-gingerol suppressed the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, increased the expression of Beclin1 to promote autophagy, and increased Bcl-2 expression to inhibit apoptosis. In addition, the damage of mitochondrial was protected, and ROS level was decreased by 6-gingerol. These firmly indicate 6-gingerol has a strong protective ability against the apoptosis caused by oxidative stress in HUVECs, and the mechanism may relate to the induction of autophagy. Our data suggest 6-gingerol may be beneficial in the prevention of atherosclerosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f64d5814f57c1f7a8037362a7405e1eTest
https://pubmed.ncbi.nlm.nih.gov/27451028Test

المؤلفون: Xiance Sun, Xiaofeng Yao, Min Chen, Chengyan Geng, Yuexia Wang, Qiujuan Li, Ya-Nan Liu, Xiaofang Liu, Guang Yang, Liping Jiang

المصدر: Toxicon : official journal of the International Society on Toxinology. 95

مصطلحات موضوعية: Autophagosome, Programmed cell death, Cell Survival, ATG5, Biology, Toxicology, Autophagy-Related Protein 5, Microscopy, Electron, Transmission, Phagosomes, Autophagy, Humans, Viability assay, Cytotoxicity, PI3K/AKT/mTOR pathway, chemistry.chemical_classification, Reactive oxygen species, Adenine, Aurovertins, Hep G2 Cells, Cell biology, chemistry, Liver, RNA Interference, Reactive Oxygen Species, Microtubule-Associated Proteins

الوصف: Citreoviridin (CIT) is one of toxic mycotoxins derived from fungal species in moldy cereals. Whether CIT exerts hepatotoxicity and the precise molecular mechanisms of CIT hepatotoxicity are not completely elucidated. In this study, the inhibitor of autophagosome formation, 3-methyladenine, protected the cells against CIT cytotoxicity, and the autophagy stimulator rapamycin further decreased the cell viability of CIT-treated HepG2 cells. Knockdown of Atg5 with Atg5 siRNA alleviated CIT-induced cell death. These finding suggested the hypothesis that autophagic cell death contributed to CIT-induced cytotoxicity in HepG2 cells. CIT increased the autophagosome number in HepG2 cells observed under a transmission electron microscope, and this effect was confirmed by the elevated LC3-II levels detected through Western blot. Reduction of P62 protein levels and the result of LC3 turnover assay indicated that the accumulation of autophagosomes in the CIT-treated HepG2 cells was due to increased formation rather than impaired degradation. The pretreatment of HepG2 cells with the ROS inhibitor NAC reduced autophagosome formation and reversed the CIT cytotoxicity, indicating that CIT-induced autophagic cell death was ROS-dependent. In summary, ROS-dependent autophagic cell death of HpeG2 cells described in this study may help to elucidate the underlying mechanism of CIT cytotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48df83aeb4a4e1a1ae9a5db829fb7452Test
https://pubmed.ncbi.nlm.nih.gov/25553592Test