المؤلفون: Xiaofeng Yao, Zhanchen Dong

المصدر: Mitochondrion. 62

مصطلحات موضوعية: Calcium metabolism, Chemistry, Endoplasmic reticulum, Biological Transport, Cell Biology, Mitochondrion, medicine.disease, Cell biology, Mitochondria, medicine.anatomical_structure, Insulin resistance, Liver, Lysosome, medicine, Molecular Medicine, Glucose homeostasis, Homeostasis, Humans, Calcium, Insulin Resistance, Molecular Biology, Ion channel

الوصف: Due to the rapid rise in the prevalence of chronic metabolic disease, more and more clinicians and basic medical researchers focus their eyesight on insulin resistance (IR), an early and central event of metabolic diseases. The occurrence and development of IR are primarily caused by excessive energy intake and reduced energy consumption. Liver is the central organ that controls glucose homeostasis, playing a considerable role in systemic IR. Decreased capacity of oxidative metabolism and mitochondrial dysfunction are being blamed as the direct reason for the development of IR. Mitochondrial Ca2+ plays a fundamental role in maintaining proper mitochondrial function and redox stability. The maintaining of mitochondrial Ca2+ homeostasis requires the cooperation of ion channels in the inner and outer membrane of mitochondria, such as mitochondrial calcium uniporter complex (MCUC) and voltage-dependent anion channels (VDACs). In addition, the crosstalk between the endoplasmic reticulum (ER), lysosome and plasma membrane with mitochondria is also significant for mitochondrial calcium homeostasis, which is responsible for an efficient network of cellular Ca2+ signaling. Here, we review the recent progression in the research about the regulation factors for mitochondrial Ca2+ and how the dysregulation of mitochondrial Ca2+ homeostasis is involved in the pathogenesis of hepatic IR, providing a new perspective for further exploring the role of ion in the onset and development of IR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfc720ddd7f470f439832cb7753808dcTest
https://pubmed.ncbi.nlm.nih.gov/34856389Test

المؤلفون: Zhanchen, Dong, Jianyu, Wang, Tianming, Qiu, Jialu, Wu, Yu, An, Xiaoxia, Shi, Xiance, Sun, Liping, Jiang, Xiaofang, Liu, Guang, Yang, Jun, Cao, Xiaofeng, Yao

المصدر: Science of The Total Environment. 825:153933

مصطلحات موضوعية: Fluorocarbons, Environmental Engineering, Voltage-Dependent Anion Channel 1, Calcium-Binding Proteins, Mitochondrial Membrane Transport Proteins, Pollution, Mitochondria, Mice, Inbred C57BL, Mice, Alkanesulfonic Acids, Liver, Tubulin, Autophagy, Animals, Humans, Environmental Chemistry, Calcium, Insulin Resistance, Cation Transport Proteins, Waste Management and Disposal

الوصف: Perfluorooctane sulfonate (PFOS), one kind of persistent organic pollutants, is associated with insulin resistance (IR) in general population. However, the exact mechanism is still obscure. In this study, we found that 50 μM PFOS caused IR in L-02 hepatocytes after 1 h, and induced autophagy and mitochondrial calcium (Ca

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59d78593d0d1936fd0b1b5d2435b6751Test
https://doi.org/10.1016/j.scitotenv.2022.153933Test

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, 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: 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: Xiaoxia Shi, Jun Cao, Chengyan Geng, Zhiguo Li, Yong Liu, Xiaofeng Yao, Qiujuan Li, Liping Jiang, Wei Lv

المصدر: Free radical biologymedicine. 130

مصطلحات موضوعية: Autophagy-Related Proteins, Apoptosis, Mitochondrion, medicine.disease_cause, Biochemistry, Downregulation and upregulation, Physiology (medical), medicine, Autophagy, Humans, Inducer, A549 cell, Membrane Potential, Mitochondrial, Chemistry, Caspase 3, Caspase 9, Cell biology, Mitochondria, Gene Expression Regulation, Neoplastic, Crosstalk (biology), Cysteine Endopeptidases, Proto-Oncogene Proteins c-bcl-2, A549 Cells, Beclin-1, Carcinogenesis, Cadmium

الوصف: Cadmium (Cd) is a highly ubiquitous detrimental metal in the environment. It is a well-known inducer of tumorigenesis, but the mechanism is not clear. In our previous study, we found that ROS-dependent Atg4B upregulation mediated Cd-induced autophagy and autophagy played an important role in Cd-induced proliferation and invasion in A549 cells. In this study, we found that Cd induced both apoptosis and autophagy in A549 cells, and apoptosis preceded autophagy. Z-VAD-FMK repressed Cd-induced LC3 and Beclin1, indicating that apoptosis was essential for Cd-induced autophagy. 3MA destroyed the recovery of mitochondrial membrane potential and increased Cd-induced CL-CASP9 and CL-CASP3 expression, suggesting that Cd-induced autophagy prevented A549 cells from apoptosis. Further study showed that Atg4B upregulation was mediated by mitochondrial dysfunction and conversely affected mitochondrial function by decreasing Bcl-2 protein expression and its localization in mitochondria, and played an important role in Cd-induced apoptosis. Moreover, Bcl-2 was involved in Cd-induced autophagy. Co-IP assay showed that Atg4B could directly bind to Bcl-2, and consequently promote disassociation of Bcl-2-Beclin1 and released autophagic protein Beclin1 to activate autophagic pathway. Taken together, our results demonstrated that the interaction of Atg4B and Bcl-2 might play an important role in Cd-induced crosstalk between apoptosis and autophagy through disassociation of Bcl-2-Beclin1. Cd-induced autophagy is apoptosis-dependent and prevents apoptotic cell death to ensure the growth and proliferation of A549 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b138bcb16e006f225ed0791caf2718f8Test
https://pubmed.ncbi.nlm.nih.gov/30458278Test

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

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

المصدر: Phytomedicine : international journal of phytotherapy and phytopharmacology. 20(8-9)

مصطلحات موضوعية: Antioxidant, Cell Survival, medicine.medical_treatment, Pharmaceutical Science, Pharmacology, Mitochondrion, medicine.disease_cause, DNA, Mitochondrial, Antioxidants, chemistry.chemical_compound, Polysaccharides, Drug Discovery, medicine, Humans, Cytotoxicity, Nootropic Agents, chemistry.chemical_classification, Medicine, East Asian Traditional, Membrane Potential, Mitochondrial, Reactive oxygen species, biology, Plant Extracts, Glutathione, Hep G2 Cells, biology.organism_classification, Mitochondria, Oxidative Stress, Complementary and alternative medicine, chemistry, Phellinus linteus, Biochemistry, Phellinus, Tacrine, Hepatocytes, Molecular Medicine, Medicine, Traditional, Reactive Oxygen Species, Oxidative stress, medicine.drug, DNA Damage

الوصف: Tacrine (THA) was the first drug licensed for the treatment of Alzheimer's disease. Unfortunately, reversible hepatotoxicity is evident in about 30% of patients and limits its clinical use. The intracellular mechanisms have not yet been elucidated. Phellinus linteus (PL) is a mushroom that has long been used as a folk medicine. In our previous study, we found that PL could decrease the reactive oxygen species (ROS) formation in HepG2 cells. Presently, protective effects of PL on tacrine-induced ROS formation and mitochondria dysfunction were evaluated. The results showed that PL significantly reduced tacrine-induced ROS production, disruption of ΔΨm, 8-OHdG formation in mitochondrial DNA, and cytotoxicity in HepG2 cells. These data suggest that PL could attenuate the cytotoxicity and mitochondria dysfunction induced by tacrine in HepG2 cells. The protection is probably mediated by an antioxidant protective mechanism. Consumption of PL may be a plausible way to prevent tacrine-induced hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c3fbec23076f081dc881694af86db14Test
https://pubmed.ncbi.nlm.nih.gov/23523257Test