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https://www.readbyqxmd.com/read/28334504/redd1-deficiency-impairs-autophagy-and-mitochondrial-biogenesis-in-articular-cartilage-and-increases-the-severity-of-experimental-osteoarthritis
#1
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Lars Plate, Jeffery W Kelly, Martin K Lotz
Objective REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritis (OA) cartilage and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. The present study investigated the effects of REDD1 deletion in vivo using a mouse model of experimental OA. Methods Severity of OA was histologically assessed in 4-month-old wild-type and in Redd1(-/-) mice subjected to surgical destabilization of the medial meniscus (DMM)...
March 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28333142/hydrogen-sulfide-promotes-autophagy-of-hepatocellular-carcinoma-cells-through-the-pi3k-akt-mtor-signaling-pathway
#2
Shanshan S Wang, Yuhan H Chen, Ning Chen, Lijun J Wang, Dexi X Chen, Honglei L Weng, Steven Dooley, Huiguo G Ding
Hydrogen sulfide (H2S), in its gaseous form, plays an important role in tumor carcinogenesis. This study investigated the effects of H2S on the cell biological functions of hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and HLE, were treated with NaHS, a donor of H2S, and rapamycin, a classic autophagy inducer, for different lengths of time. Western blotting, immunofluorescence, transmission electron microscopy (TEM), scratch assay, CCK-8 and flow cytometric analysis were carried out to examine the effects of H2S on HCC autophagy, cell behavior and PI3K/Akt/mTOR signaling...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28323964/dysregulated-autophagy-in-hepatocytes-promotes-bisphenol-a-bpa-induced-hepatic-lipid-accumulation-in-male-mice
#3
Shumin Yang, Ting Li, Aipin Zhang, Rufei Gao, Chuan Peng, Lulu Liu, Qingfeng Cheng, Mei Mei, Ying Song, Xiaojiao Xiang, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Context: Accumulating evidence suggests that bisphenol A (BPA) exposure is associated with nonalcoholic fatty liver disease. Disruption of autophagy causes lipid accumulation in hepatocytes. Whether and how BPA regulates autophagy remains to be explored. Objective: We investigated the effect of BPA on autophagy in hepatocytes and examined the influence of BPA-regulated autophagy on hepatic lipid accumulation. Design: Male CD1 mice were treated with BPA for eight weeks, followed by histological and biochemical evaluation of liver lipids and autophagy...
February 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320103/paeoniflorin-ameliorates-ages-induced-mesangial-cell-injury-through-inhibiting-rage-mtor-autophagy-pathway
#4
Juan Chen, Di Zhao, Maomao Zhu, Minghua Zhang, Xuefeng Hou, Wenbo Ding, Shuai Sun, Weiquan Bu, Liang Feng, Shiping Ma, Xiaobin Jia
Glomerular mesangial cell plays a vital role in diabetic nephropathy (DN). Recent research has demonstrated that autophagy involved in the development of DN. Paeoniflorin (PF), a monoterpene glucoside, has been proved to attenuate advanced glycation end products (AGEs)-induced mesangial cell injury. However, the regulatory mechanism of PF on autophagy in mesangial cell remains unclear. The aim of this study was to explore the effect of PF on autophagy in AGEs-induced mesangial cell dysfunction. In this study, the leakage of the lactic dehydrogenase (LDH) into the extracellular medium was measured by LDH kit...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320092/inhibition-of-pi3k-akt-mtor-signaling-pathway-promotes-autophagy-of-articular-chondrocytes-and-attenuates-inflammatory-response-in-rats-with-osteoarthritis
#5
Jian-Feng Xue, Zhong-Min Shi, Jian Zou, Xiao-Lin Li
OBJECTIVE: This study aims to explore the relationship between PI3K/AKT/mTOR signaling pathway and autophagy of articular chondrocytes in rats with osteoarthritis (OA). METHODS: Rat articular chondrocytes were isolated and cultured, and then induced by protein inhibitors of PI3K/AKT/mTOR signaling pathway. Chondrocytes were assigned into blank group, IL-1β induction group (IL-1β group), PI3K inhibitor+IL-1β induction group (PI3Ki+IL-1β group), AKT inhibitor+IL-1β induction group (AKTi+IL-1β group) and mTOR inhibitor+IL-1β induction group (mTORi+IL-1β group)...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#6
Christian W Keller, Monica Loi, Svenja Ewert, Isaak Quast, Romina Theiler, Monique Gannagé, Christian Münz, Gennaro De Libero, Stefan Freigang, Jan D Lünemann
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane...
March 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28296196/sirt6-reduces-macrophage-foam-cell-formation-by-inducing-autophagy-and-cholesterol-efflux-under-ox-ldl-condition
#7
Jiangping He, Guangya Zhang, Qi Pang, Cong Yu, Jie Xiong, Jing Zhu, Fengling Chen
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28296000/novel-application-of-localized-nanodelivery-of-anti-il6-protects-organ-transplant-from-ischemia-reperfusion-injuries
#8
Zhabiz Solhjou, Mayuko Uehara, Baharak Bahmani, Omar H Maarouf, Takaharu Ichimura, Craig R Brooks, Wanlong Xu, Mine Yilmaz, Abdala Elkhal, Stefan G Tullius, Indira Guleria, Martina McGrath, Reza Abdi
Ischemia reperfusion injury (IRI) evokes intra-graft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DC). While autophagy is a survival mechanism for ischemic DC, it also augments their production of IL6. Allograft derived dendritic cells (ADDC) lacking autophagy related gene 5 (Atg5) showed higher death rates post-transplantation...
March 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28294332/autophagy-mediates-cytotoxicity-of-human-colorectal-cancer-cells-treated-with-garcinielliptone-fc
#9
Shen-Jeu Won, Cheng-Hsin Yen, Ting-Yu Lin, Ya-Fen Jiang-Shieh, Chun-Nan Lin, Jyun-Ti Chen, Chun-Li Su
The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28294316/knockout-of-atg5-leads-to-malignant-cell-transformation-and-resistance-to-src-family-kinase-inhibitor-pp2
#10
Sung-Hee Hwang, Byeal-I Han, Michael Lee
Autophagy can either promote or inhibit cell death in different cellular contexts. In this study, we investigated the role of autophagy in ATG5 knockout (KO) cell line established using CRISPR/Cas9 system. In ATG5 KO cells, RT-PCR and immunoblot of LC3 confirmed the functional gene knockout. We found that knockout of ATG5 significantly increased proliferation of NIH 3T3 cells. In particular, autophagy deficiency enhanced susceptibility to cellular transformation as determined by an in vitro clonogenic survival assay and a soft agar colony formation assay...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28294157/alkaline-ceramidase-2-is-a-novel-direct-target-of-p53-and-induces-autophagy-and-apoptosis-through-ros-generation
#11
Yitao Wang, Chunxue Zhang, Yuelei Jin, Wang, Qing He, Zhu Liu, Qing Ai, Yunlong Lei, Yi Li, Fangzhou Song, Youquan Bu
ACER2 is a critical sphingolipid metabolizing enzyme, and has been shown to be remarkably up-regulated following various stimuli such as DNA damage. However, the transcriptional regulatory mechanism of ACER2 gene and its potential role in the regulation of autophagy remain unknown. In this study, we have for the first time identified the human ACER2 gene promoter, and found that human ACER2 transcription is directly regulated by p53 and ACER2 is implicated in the induction of autophagy as well as apoptosis...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292026/catalpol-protects-glucose-deprived-rat-embryonic-cardiac-cells-by-inducing-mitophagy-and-modulating-estrogen-receptor
#12
Chao Lin, Ying Lu, Xiaojing Yan, Xiang Wu, Meiyu Kuai, Xin Sun, Qi Chen, Xueyun Kong, Zhaoguo Liu, Yuping Tang, Yi Jing, Yu Li, Qichun Zhang, Huimin Bian
Catalpol, a bioactive component from Rehmannia glutinosa (Di Huang), has been widely used to protect cardiomyocytes against myocardial ischemia. The aim of the present study was to investigate the anti-apoptotic and anti-oxidative effects of Catalpol on glucose-starved H9c2 cells for cardio-protection and to elucidate the underlying mechanisms. Here, we showed that Catalpol protected the glucose-starved H9c2 cells through reducing apoptosis and attenuating oxidative damage. Moreover, the increases of autophagic lysosomes, LC3, autophagic flux and autophagic vacuole were observed in Catalpol-treated cells using flow cytometer and fluorescence microscope...
March 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28292022/the-effects-of-the-long-non-coding-rna-malat-1-regulated-autophagy-related-signaling-pathway-on-chemotherapy-resistance-in-diffuse-large-b-cell-lymphoma
#13
Li-Juan Li, Ye Chai, Xiao-Jia Guo, Song-Lin Chu, Lian-Sheng Zhang
OBJECTIVE: Our study aimed to investigate the effects of the long non-coding RNA MALAT-1 (lncRNA MALAT-1) regulated autophagy-related signaling pathway on chemotherapy resistance in diffuse large B-cell lymphoma (DLBCL). METHODS: Human normal B lymphocytes (IM-9I) and DLBCL cell lines (Farage, Pfeiffer, Raji, Daud, Ly1, Ly3, Ly8 and Ly10) were chosen for our experiment. qRT-PCR was applied to detect the expression of lncRNA MALAT-1 in each DLBCL cell line. Farage and Daud cells were induced to be drug-resistant using 0...
March 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28289410/autophagy-and-autophagy-related-proteins-in-cns-autoimmunity
#14
REVIEW
Christian W Keller, Jan D Lünemann
Autophagy comprises a heterogeneous group of cellular pathways that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients, and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate and adaptive immune responses and to shape CD4(+) T cell immunity through delivery of peptides to major histocompatibility complex (MHC) class II-containing compartments (MIICs). Individual autophagy proteins additionally modulate expression of MHC class I molecules for CD8(+) T cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28282266/autophagy-is-dispensable-for-kmt2a-mll-mllt3-af9-aml-maintenance-and-anti-leukemic-effect-of-chloroquine
#15
Xiaoyi Chen, Jason Clark, Mark Wunderlich, Cuiqing Fan, Ashley Davis, Song Chen, Jun-Lin Guan, James C Mulloy, Ashish Kumar, Yi Zheng
Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28279708/genetic-analysis-of-the-atg16l1-gene-promoter-in-sporadic-parkinson-s-disease
#16
Lixia Wang, Jian Huang, Shuchao Pang, Xianyun Qin, Ziyou Qi, Robert G Hawley, Bo Yan
Parkinson's disease (PD) is a common and progressive neurodegenerative disease in which the majority of cases arise sporadically. Sporadic PD is caused by the interactions of genetic and environmental factors. To date, genetic causes for sporadic PD remain largely unknown. Autophagy, a highly conserved cellular process, has been implicated in PD pathogenesis. We speculated that genetic variants in autophagy-related genes (ATG) that regulate gene expression may contribute to PD development. In our previous studies, we have identified several functional DNA sequence variants (DSVs) in the ATG5, ATG7 and LC3 genes in sporadic PD patients...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28276509/suppression-of-autophagy-by-mycophenolic-acid-contributes-to-inhibition-of-hcv-replication-in-human-hepatoma-cells
#17
Shoucai Fang, Jinming Su, Bingyu Liang, Xu Li, Yu Li, Junjun Jiang, Jiegang Huang, Bo Zhou, Chuanyi Ning, Jieliang Li, Wenzhe Ho, Yiping Li, Hui Chen, Hao Liang, Li Ye
Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274318/-knockdown-of-atg5-enhances-the-sensitivity-of-human-renal-carcinoma-cells-to-sunitinib
#18
Peng Li, Qi Han, Ming Tang, Keqin Zhang
Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28259927/autophagy-induction-in-the-skeletal-myogenic-differentiation-of-human-tonsil-derived-mesenchymal-stem-cells
#19
Saeyoung Park, Yoonyoung Choi, Namhee Jung, Jieun Kim, Seiyoon Oh, Yeonsil Yu, Jung-Hyuck Ahn, Inho Jo, Byung-Ok Choi, Sung-Chul Jung
Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation and are thus a valuable source for the replacement of diseased or damaged organs. Previously, we reported that the tonsils can be an excellent reservoir of MSCs for the regeneration of skeletal muscle (SKM) damage. However, the mechanisms involved in the differentiation from tonsil-derived MSCs (T-MSCs) to myocytes via myoblasts remain unclear. To clarify these mechanisms, we analyzed gene expression profiles of T-MSCs during differentiation into myocytes compared with human skeletal muscle cells (hSKMCs)...
February 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28258963/interferon-%C3%AE-induced-insufficient-autophagy-contributes-to-p62-dependent-apoptosis-of-epithelial-cells-in-chronic-rhinosinusitis-with-nasal-polyps
#20
Bao-Feng Wang, Ping-Ping Cao, Zhi-Chao Wang, Zhi-Yong Li, Zhe-Zheng Wang, Jin Ma, Bo Liao, Yi-Ke Deng, Xiao-Bo Long, Kai Xu, Heng Wang, Hai Wang, Ming Zeng, Xiang Lu, Zheng Liu
BACKGROUND: Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP). METHODS: The expression of autophagic proteins [microtubule-associated protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules [cysteine-aspartic protease-3 and 8, and poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting...
March 4, 2017: Allergy
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