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https://www.readbyqxmd.com/read/29328502/hepatocellular-carcinoma-related-cyclin-d1-is-selectively-regulated-by-autophagy-degradation-system
#1
Shan-Ying Wu, Sheng-Hui Lan, Shang-Rung Wu, Yen-Chi Chiu, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Chung-Yi Li, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu
Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic miR-224 to prevent HCC. Therefore, in the present study we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in the tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development...
January 12, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29326381/b1a-b-cells-require-autophagy-for-metabolic-homeostasis-and-self-renewal
#2
Alexander J Clarke, Thomas Riffelmacher, Daniel Braas, Richard J Cornall, Anna Katharina Simon
Specific metabolic programs are activated by immune cells to fulfill their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis...
January 11, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29316373/tanshinone-iia-induces-cell-death-via-beclin-1-dependent-autophagy-in-oral-squamous-cell-carcinoma-scc-9-cell-line
#3
Ye Qiu, Conghua Li, Qinhua Wang, Xingqi Zeng, Ping Ji
Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis- and autophagy-inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC-9 was used for in vitro assays and induction in an OSCC xenograft mouse model...
January 6, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29311760/mir-20a-5p-suppresses-tumor-proliferation-by-targeting-autophagy-related-gene-7-in-neuroblastoma
#4
Yongbo Yu, Jie Zhang, Yaqiong Jin, Yeran Yang, Jin Shi, Feng Chen, Shujing Han, Ping Chu, Jie Lu, Huanmin Wang, Yongli Guo, Xin Ni
Background: Neuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood. Methods: Quantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting)...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29311680/inhibition-of-insulin-resistance-by-pge1-via-autophagy-dependent-fgf21-pathway-in-diabetic-nephropathy
#5
Wei Wei, Xing-Rong An, Shi-Jie Jin, Xiao-Xue Li, Ming Xu
Insulin resistance is a critical process in the initiation and progression of diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311554/oxidation-of-atg3-and-atg7-mediates-inhibition-of-autophagy
#6
Karen Frudd, Thomas Burgoyne, Joseph Robert Burgoyne
Macroautophagy (autophagy) is a crucial cellular stress response for degrading defective macromolecules and organelles, as well as providing bioenergetic intermediates during hypoxia and nutrient deprivation. Here we report a thiol-dependent process that may account for impaired autophagy during aging. This is through direct oxidation of key autophagy-related (Atg) proteins Atg3 and Atg7. When inactive Atg3 and Atg7 are protected from oxidation due to stable covalent interaction with their substrate LC3. This interaction becomes transient upon activation of Atg3 and Atg7 due to transfer of LC3 to phosphatidylethanolamine (lipidation), a process crucial for functional autophagy...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29306208/alpha-2-dihydroxy-4-4-dimethoxydihydrochalcone-inhibits-cell-proliferation-invasion-and-migration-in-gastric-cancer-in-part-via-autophagy
#7
Boshun Wan, Junqiu Zhu, Qing Chang, Haihua Zhou, Zhan Shi, Li Min, YueJiao Cai, Honggeng Guan
Gastric cancer is a leading cause of mortality worldwide. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone is a type of limonoid mainly isolated from Cedrela odorata (Meliaceae) that has been shown to suppress cell proliferation in several human carcinoma cell lines. In this study, we investigated the anti-cancer ability of alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone and its underlying mechanism in MKN45 cells. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone induced excess reactive oxygen species (ROS) accumulation...
January 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29301200/bombyx-mori-nuclear-polyhedrosis-virus-bmnpv-induces-host-cell-autophagy-to-benefit-infection
#8
La Wang, Qin Xiao, Xiao-Lin Zhou, Yan Zhu, Zhan-Qi Dong, Peng Chen, Min-Hui Pan, Cheng Lu
Bombyx mori nuclear polyhedrosis virus (BmNPV) is an important pathogen of silkworms. Despite extensive studies in recent decades, the interaction between BmNPV and host cells is still not clearly understood. Autophagy is an intrinsic innate immune mechanism and it controls infection autonomously in virus-infected cells. In this study, we found that BmNPV infection could trigger autophagy, as demonstrated by the formation of autophagosomes, fluorescent Autophagy-related gene 8-Green Fluorescent Protein (ATG8-GFP) punctate, and lipidated ATG8...
December 30, 2017: Viruses
https://www.readbyqxmd.com/read/29288662/autophagy-dysregulation-caused-by-apom-deficiency-plays-an-important-role-in-liver-lipid-metabolic-disorder
#9
Xiao Zhang, Puhong Zhang, Jialin Gao, Qiang Huang
Autophagy is thought to be a key mechanism in maintaining the balance of liver lipid metabolism. However, the relationship between apolipoprotein M (ApoM) and autophagy has not been reported, and the role of ApoM in triglyceride metabolism is still unclear. In this study, we investigated the correlation between ApoM and autophagy and liver triglyceride metabolism in ApoM-knockout animal and cellular models. First, we observed that spontaneous hepatic steatosis developed in the liver of adult ApoM-/- mice, which was presented as the accumulation of large quantities of lipid droplets in hepatocytes under electron microscopy; Oil Red O staining showed significant accumulation of triglycerides...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29277787/phenoxodiol-increases-cisplatin-sensitivity-in-ovarian-clear-cancer-cells-through-xiap-down-regulation-and-autophagy-inhibition
#10
Morikazu Miyamoto, Masashi Takano, Tadashi Aoyama, Hiroaki Soyama, Hiroki Ishibashi, Kento Kato, Hideki Iwahashi, Kazuki Takasaki, Mika Kuwahara, Hiroko Matuura, Takahiro Sakamoto, Tomoyuki Yoshikawa, Kenichi Furuya
BACKGROUND/AIM: To investigate whether XIAP down-regulation and autophagy inhibition sensitize ovarian clear cell cancer cells to cisplatin. MATERIALS AND METHODS: The ovarian clear cancer cell line KK was used for in vitro analysis. Hydroxychloroquine (HCQ) and phenoxodiol (PXD) or embelin were used as autophagy and XIAP inhibitors, respectively. Non-specific and XIAP-specific siRNAs were transfected using Lipofectamine. Cytotoxicity was assessed by MTT assays...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29273589/attenuation-of-perk-enhances-glucose-stimulated-insulin-secretion-in-islets
#11
Min Joo Kim, Se Hee Min, Seon Young Shin, Mi Na Kim, Hakmo Lee, Jin Young Jang, Sun-Whe Kim, Kyong Soo Park, Hye Seung Jung
PERK is a pancreatic endoplasmic reticulum (ER) kinase. Its complete deletion in pancreatic β cells induces insulin deficiency; however, the effects of partial Perk suppression are unclear. We investigated the effect of partial PERK suppression using the specific PERK inhibitors GSK2606414 and GSK2656157. Low dose GSK2606414 treatment for 24 h enhanced glucose-stimulated insulin secretion (GSIS), islet insulin content, and calcium transit in mouse (at 40 nM) and human (at 50~100 nM) pancreatic islets. GSK2606414 also induced the expression of the ER chaperone BiP and the release of calcium from the ER...
December 22, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29273297/loss-of-vascular-smooth-muscle-cell-autophagy-exacerbates-angiotensin-ii-associated-aortic-remodeling
#12
Azza Ramadan, Krishna K Singh, Adrian Quan, Pamela J Plant, Mohammed Al-Omran, Hwee Teoh, Subodh Verma
OBJECTIVE: The pathophysiologic processes of abdominal aortic aneurysms (AAAs) and atherosclerosis often intersect. Given that anomalies in vascular smooth muscle cell (SMC) autophagy have been noted in models of atherosclerosis, we sought to evaluate the potential role that SMC autophagy may play in the initiation and progression of AAAs. METHODS: Studies were conducted in ATG7flx/flxSM22α-Cretg/+ (SMC ATG7 knockout [SMC-ATG7-KO]) and ATG7WT/WT; SM22α-Cretg/+ (SMC ATG7 wild-type [SMC-ATG7-WT]) littermates that were continuously infused with angiotensin II (Ang II; 1...
December 19, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29259263/clinical-implications-of-the-autophagy-core-gene-variations-in-advanced-lung-adenocarcinoma-treated-with-gefitinib
#13
Jupeng Yuan, Nasha Zhang, Longbin Yin, Hui Zhu, Li Zhang, Liqing Zhou, Ming Yang
EGFR-TKIs show dramatic treatment benefits for advanced lung adenocarcinoma patients with activating EGFR mutations. Considering the essential role of autophagy in EGFR-TKIs treatments, we hypothesized that genetic variants in autophagy core genes might contribute to outcomes of advanced lung adenocarcinoma treated with gefitinib. We systematically examined 27 potentially functional genetic polymorphisms in 11 autophagy core genes among 108 gefitinib-treated advanced lung adenocarcinoma patients. We found that ATG10 rs10036653, ATG12 rs26538, ATG16L1 rs2241880 and ATG16L2 rs11235604 were significantly associated with survival of lung adenocarcinoma patients (all P < 0...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#14
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29247839/%C3%AE-solanine-impairs-oocyte-maturation-and-quality-by-inducing-autophagy-and-apoptosis-and-changing-histone-modifications-in-a-pig-model
#15
Tao Lin, Reza K Oqani, Jae Eun Lee, Jeong Won Kang, So Yeon Kim, Eun Seok Cho, Yong Dae Jeong, Jun Jong Baek, Dong Il Jin
In this study, we used a pig model to investigate the effects of α-solanine (a natural toxin found mainly in potato sprouts) on oocyte maturation, quality and subsequent embryonic development. We found that α-solanine (10 μM) disturbed meiotic resumption and increased abnormal spindle formation and altered the cortical granule (CG) distribution compared with the untreated group. α-Solanine triggered autophagy and apoptosis by increasing the expressions of autophagy-related genes (LC3, ATG7, and LAMP2) and apoptotic related genes (BAX and CASP3)...
December 13, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/29237558/atg7-activates-an-autophagy-essential-ubiquitin-like-protein-atg8-through-multi-step-recognition
#16
Masaya Yamaguchi, Kenji Satoo, Hironori Suzuki, Yuko Fujioka, Yoshinori Ohsumi, Fuyuhiko Inagaki, Nobuo N Noda
Atg8 is a unique ubiquitin-like protein that is covalently conjugated with a phosphatidylethanolamine through reactions similar to ubiquitination and plays essential roles in autophagy. Atg7 is the E1 enzyme for Atg8, and it activates the C-terminal Gly116 of Atg8 using ATP. Here, we report the crystal structure of Atg8 bound to the C-terminal domain of Atg7 in an unprecedented mode. Atg8 neither contacts with the central β-sheet nor binds to the catalytic site of Atg7, both of which were observed in previously reported Atg7-Atg8 structures...
December 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29234488/sirt6-histone-deacetylase-functions-as-a-potential-oncogene-in-human-melanoma
#17
Liz Mariely Garcia-Peterson, Mary Ann Ndiaye, Chandra K Singh, Gagan Chhabra, Wei Huang, Nihal Ahmad
Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin SIRT6 in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant SIRT6 mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant SIRT6 overexpression in human melanoma tissues...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29228719/levels-of-leydig-cell-autophagy-regulate-the-fertility-of-male-naked-mole-rats
#18
Wenjing Yang, Li Li, Xiaofeng Huang, Guanghan Kan, Lifang Lin, Jishuai Cheng, Chen Xu, Wei Sun, Wei Cong, Shanmin Zhao, Shufang Cui
Fertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs. This alteration was visualised as a significant decrease in the levels of autophagy-related gene 7 (Atg7), Atg5, microtubule-associated protein 1A/B light chain 3 (LC3-II/I) and the number of autophagosomes and an increase in P62 levels using Western blotting analyses...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228691/berberine-attenuated-pro-inflammatory-factors-and-protect-against-neuronal-damage-via-triggering-oligodendrocyte-autophagy-in-spinal-cord-injury
#19
Hongyu Wang, Chang Liu, Xifan Mei, Yang Cao, Zhanpeng Guo, Yajiang Yuan, Ziming Zhao, Changwei Song, Yue Guo, Zhaoliang Shen
Berberine exerts neuroprotective effect in neuroinflammation and neurodegeneration disease. However, berberine effect in acute spinal cord injury is yet to be elucidated. Herein, we investigated the neuroprotective effect of berberine in spinal cord injury (SCI). Sprague-Dawley rats were subjected to SCI by an intraperitoneal injection of berberine post-injury. The neurobehavioral recovery, cytokines of pro-inflammatory factors (TNF-α and IL-1β), autophagy-related proteins (LC3B, ATG16L, ATG7), and apoptosis-related protein cleaved caspase-3 were determined...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228587/chronic-myeloid-leukemia-progenitor-cells-require-autophagy-when-leaving-hypoxia-induced-quiescence
#20
Angela Ianniciello, Pierre-Yves Dumas, Claire Drullion, Amélie Guitart, Arnaud Villacreces, Yan Peytour, Jean Chevaleyre, Philippe Brunet de la Grange, Isabelle Vigon, Vanessa Desplat, Muriel Priault, Persio Dello Sbarba, Zoran Ivanovic, François-Xavier Mahon, Jean-Max Pasquet
Albeit tyrosine kinase inhibitors anti-Abl used in Chronic Myeloid Leukemia (CML) block the deregulated activity of the Bcr-Abl tyrosine kinase and induce remission in 90% of patients, they do not eradicate immature hematopoietic compartments of leukemic stem cells. To elucidate if autophagy is important for stem cell survival and/or proliferation, we used culture in low oxygen concentration (0.1% O2 for 7 days) followed back by non-restricted O2 supply (normoxic culture) to mimic stem cell proliferation and commitment...
November 14, 2017: Oncotarget
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