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Xuehua Shao, Duo Lai, Ling Zhang, Hanhong Xu
Azadirachtin is one of the most effective botanical insecticides and has been widely used in pest control. Toxicological reports show that azadirachtin can induce apoptosis in various insect cell lines. However, studies of azadirachtin-induced autophagy in cultured insect cells are lacking. This study reports that azadirachtin A significantly inhibits cell proliferation by inducing autophagic and apoptotic cell death in Spodoptera litura cultured cell line (SL-1 cell). Characteristic autophagolysosome and Atg8-PE (phosphatidylethanolamine) accumulation were observed by electron microscopy and western blotting, indicating that azadirachtin triggered autophagy in SL-1 cell...
October 18, 2016: Scientific Reports
Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara
Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62 and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically-induced liver injury...
October 17, 2016: Journal of Cellular Physiology
Kirsten A M White, Li Luo, Todd A Thompson, Salina Torres, Chien-An Andy Hu, Nancy E Thomas, Jenna Lilyquist, Hoda Anton-Culver, Stephen B Gruber, Lynn From, Klaus J Busam, Irene Orlow, Peter A Kanetsky, Loraine D Marrett, Richard P Gallagher, Lidia Sacchetto, Stefano Rosso, Terence Dwyer, Anne E Cust, Colin B Begg, Marianne Berwick
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0...
October 17, 2016: Cancer Medicine
Pervez Ahmed Khoso, Tingru Pan, Na Wan, Zijiang Yang, Ci Liu, Shu Li
The aim of the present study was to investigate the effects of selenium (Se) deficiency on autophagy-related genes and on ultrastructural changes in the spleen, bursa of Fabricius, and thymus of chickens. The Se deficiency group was fed a basal diet containing Se at 0.033 mg/kg and the control group was fed the same basal diet containing Se at 0.15 mg/kg. The messenger RNA (mRNA) levels of the autophagy genes microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin 1, dynein, autophagy associated gene 5 (ATG5), and target of rapamycin complex 1 (TORC1) were assessed using real-time qPCR...
October 15, 2016: Biological Trace Element Research
Cheng Wen Yao, Kyoung Ah Kang, Mei Jing Piao, Yea Seong Ryu, Pattage Madushan Dilhara Jayatissa Fernando, Min Chang Oh, Jeong Eon Park, Kristina Shilnikova, Soo-Young Na, Seung Uk Jeong, Sun-Jin Boo, Jin Won Hyun
We investigated the role of autophagy in SNUC5/5-FUR, 5-fluorouracil (5-FU) resistant SNUC5 colon cancer cells. SNUC5/5-FUR cells exhibited low level of autophagy, as determined by light microscopy, confocal microscopy, and flow cytometry following acridine orange staining, and the decreased level of GFP-LC3 puncta. In addition, expression of critical autophagic proteins such as Atg5, Beclin-1 and LC3-II and autophagic flux was diminished in SNUC5/5-FUR cells. Whereas production of reactive oxygen species (ROS) was significantly elevated in SNUC5/5-FUR cells, treatment with the ROS inhibitor N-acetyl cysteine further reduced the level of autophagy...
October 17, 2016: Biomolecules & Therapeutics
Min Huang, Jacqueline S Garcia, Daniel Thomas, Li Zhu, Le Xuan Truong Nguyen, Steven M Chan, Ravindra Majeti, Bruno C Medeiros, Beverly S Mitchell
The mechanisms underlying activation of the BET pathway in AML cells remain poorly understood. We have discovered that autophagy is activated in acute leukemia cells expressing mutant nucleophosmin 1 (NPMc+) or MLL-fusion proteins. Autophagy activation results in the degradation of NPM1 and HEXIM1, two negative regulators of BET pathway activation. Inhibition of autophagy with pharmacologic inhibitors or through knocking down autophagy-related gene 5 (Atg5) expression increases the expression of both NPM1 and HEXIM1...
October 6, 2016: Oncotarget
Areerat Kunanopparat, Ingorn Kimkong, Tanapat Palaga, Pisit Tangkijvanich, Boonchoo Sirichindakul, Nattiya Hirankarn
AIM: To investigate autophagy-related genes, particularly ATG12, in apoptosis and cell cycle in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and non-HBV-HCC cell lines. METHODS: The expression of autophagy-related genes in HBV-associated hepatocellular carcinoma and non-HBV-HCC cell lines and human liver tissues was examined by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting. The silencing of target genes was used to examine the function of various genes in apoptosis and cell cycle progression...
October 7, 2016: World Journal of Gastroenterology: WJG
Qing-Hua Cao, Fang Liu, Zu-Li Yang, Xin-Hui Fu, Zi-Huan Yang, Quentin Liu, Lei Wang, Xiang-Bo Wan, Xin-Juan Fan
Autophagy-related (ATG) genes contributed to tumorigenesis and cancer progression. This study aims to investigate the expression of ATG proteins and their clinicopathological significance in gastric cancer. Nine well-known ATG proteins, (ULK1, Beclin 1, ATG3, ATG5, ATG7, ATG9, ATG10, ATG12 and LC3B) and p62/SQSTM1, which represented key regulators that participated in whole autophagosomes stepwise processes, were detected in a large cohort of 352 primary gastric cancer patients. Among these 352 patients, 117 cases were randomly assigned to the training set to detect the clinicopathological value of ATG proteins, and another 235 patients were used as the testing set for further validation...
2016: American Journal of Translational Research
Arpita Baisantry, Sagar Bhayana, Christoph Wrede, Jan Hegermann, Hermann Haller, Anette Melk, Roland Schmitt
Autophagy and senescence are two distinct pathways that are importantly involved in acute kidney injury and renal repair. Recent data indicate that the two processes might be interrelated. To investigate the potential link between autophagy and senescence in the kidney we isolated primary tubular epithelial cells (PTEC) from wild-type mice and monitored the occurrence of cellular senescence during autophagy activation and inhibition. We found that the process of cell isolation and transfer into culture was associated with a strong basal autophagic activation in PTEC...
October 7, 2016: Cell Cycle
R Santarelli, M Granato, G Pentassuglia, V Lacconi, M S Gilardini Montani, R Gonnella, M Tafani, M R Torrisi, A Faggioni, M Cirone
We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism put in place by KSHV to escape from immune control...
October 7, 2016: Autophagy
Ki Won Lee, Hyung Won Ryu, Sang-Seok Oh, Soojong Park, Hamadi Madhi, Jiyun Yoo, Ki-Hun Park, Kwang Dong Kim
Melanogenesis is a key pathway for the regulation of skin pigmentation and the development of skin-lightening/whitening drugs or cosmetics. In this study, we found that β-mangostin from seedcases of Garcinia mangostana inhibited α-melanocyte-stimulating hormone (α-MSH)-mediated melanogenesis in B16F10 melanoma cells and a three-dimensional human skin model. β-Mangostin significantly inhibited the protein level of tyrosinase induced by α-MSH in UPS (ubiquitin proteasome system)-independent and lysosome-dependent manner...
October 7, 2016: Experimental Dermatology
Yaning Zhang, Yufeng Li, Wentao Yuan, Yuting Xia, Yijuan Shen
Haemophilus parasuis (H. parasuis) is a common commensal Gram-negative extracellular bacterium in the upper respiratory tract of swine, which can cause Glässer's disease in stress conditions. Research on the pathogenicity of H. parasuis has mainly focused on immune evasion and bacterial virulence factors, while few studies have examined the interactions of H. parasuis and its host. Autophagy is associated with the replication and proliferation of many pathogenic bacteria, but whether it plays a role during infection by H...
2016: Frontiers in Microbiology
Tomohiko Fukuda, Katsutoshi Oda, Osamu Wada-Hiraike, Kenbun Sone, Kanako Inaba, Yuji Ikeda, Chinami Makii, Aki Miyasaka, Tomoko Kashiyama, Michihiro Tanikawa, Takahide Arimoto, Tetsu Yano, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
Resveratrol (RSV), a polyphenolic compound derived from red wine, inhibits the proliferation of various types of cancer. RSV induces apoptosis in cancer cells, while enhancing autophagy. Autophagy promotes cancer cell growth by driving cellular metabolism, which may counteract the effect of RSV. The present study aimed to elucidate the correlation between RSV and autophagy and to examine whether autophagy inhibition may enhance the antitumor effect of RSV in endometrial cancer cells. Cell proliferation, cell cycle progression and apoptosis were examined, following RSV exposure, by performing MTT assays, flow cytometry and annexin V staining, respectively, in an Ishikawa endometrial cancer cell line...
October 2016: Oncology Letters
Kimberly Maxfield, Jennifer Macion, Hariprasad Vankayalapati, Angelique W Whitehurst
Triple negative breast cancer (TNBC) is a highly heterogeneous disease with multiple, distinct molecular subtypes that exhibit unique transcriptional programs and clinical progression trajectories. Despite knowledge of the molecular heterogeneity of the disease, most patients are limited to generic, indiscriminate treatment options: cytotoxic chemotherapy, surgery and radiation. To identify new intervention targets in TNBC, we used large-scale, loss of function screening to identify molecular vulnerabilities among different oncogenomic backgrounds...
October 3, 2016: Molecular and Cellular Biology
Saori R Yoshii, Akiko Kuma, Takumi Akashi, Taichi Hara, Atsushi Yamamoto, Yoshitaka Kurikawa, Eisuke Itakura, Satoshi Tsukamoto, Hiroshi Shitara, Yoshinobu Eishi, Noboru Mizushima
Autophagy is a cytoplasmic degradation system that is important for starvation adaptation and cellular quality control. Previously, we reported that Atg5-null mice are neonatal lethal; however, the exact cause of their death remains unknown. Here, we show that restoration of ATG5 in the brain is sufficient to rescue Atg5-null mice from neonatal lethality. This suggests that neuronal dysfunction, including suckling failure, is the primary cause of the death of Atg5-null neonates, which would further be accelerated by nutrient insufficiency due to a systemic failure in autophagy...
October 10, 2016: Developmental Cell
Hong-Yi Zhang, Ya-Dong Ma, Ye Zhang, Jie Cui, Zi-Ming Wang
AIM: To evaluate the expression levels and prognostic significance of autophagy-related markers, UNC-51-like kinase1 (ULK1), Beclin1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 5 (ATG5) and mitochondrion-associated autophagy inhibitor, LRPPRC, in patients with metastatic prostate cancer (PCa) after androgen deprivation therapy (ADT). METHODS: Expressions of ULK1, Beclin1, LC3, ATG5 and LRPPRC were assessed by immunohistochemical examination in 198 patients with metastatic PCa who were receiving ADT (goserelin and bicalutamide)...
September 27, 2016: Journal of Clinical Pathology
Xiao Liu, Haihong Qin, Jinhua Xu
Autophagy is a highly conserved catabolic process, whereby unwanted cytoplasmic contents are enclosed by the double-membrane autophagosomes and delivered to the lysosomes for degradation. It is responsible for the recycling of nutrients and cellular components, thus playing a pivotal role in maintaining cellular homeostasis as well as cell survival during stress conditions. Perturbations in autophagy are implicated in multiple diseases, such as cancers and neuro-degeneration diseases. Recent studies demonstrate that autophagy may participate in almost every step of immune responses, including pathogen recognition, antigen processing and presentation, immune cell development and function, and immunoregulation...
September 24, 2016: International Immunopharmacology
Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Sone, Shimpei Uraguchi, Masako Kiyono
Methylmercury (MeHg) is a widespread environmental pollutant and causes a serious hazard to health worldwide. However, molecular mechanisms underlying MeHg toxicity remain elusive. We show that MeHg reduced mouse embryonic fibroblast (MEF) viability in a dose-dependent manner. Furthermore, MeHg treatment increased levels of autophagy markers LC3-II and p62, possibly by acting on the MAPKs signaling pathway in several cell types. MeHg exposure elevated the number of LC3 puncta in stable GFP-LC3 MEFs and the number of autophagic vacuoles...
September 22, 2016: Toxicology Letters
Sung-Chul Lim, Ho Jong Jeon, Keun Hong Kee, Mi Ja Lee, Ran Hong, Song Iy Han
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, a number of cancer cells demonstrate TRAIL resistance. To date, various molecular targets leading to TRAIL resistance have been elucidated by many researchers, but the mechanisms involved are still not fully understood. In the present study, we obtained TRAIL-resistant cells from the human hepatocellular carcinoma cell line HepG2 by exposing cells to recombinant human TRAIL (rhTRAIL), and determined a mechanism for TRAIL resistance...
September 20, 2016: International Journal of Oncology
Chih-Kang Chiang, Ching-Chia Wang, Tien-Fong Lu, Kuo-How Huang, Meei-Ling Sheu, Shing-Hwa Liu, Kuan-Yu Hung
Advanced glycation end-products (AGEs)-induced mesangial cell death is one of major causes of glomerulus dysfunction in diabetic nephropathy. Both endoplasmic reticulum (ER) stress and autophagy are adaptive responses in cells under environmental stress and participate in the renal diseases. The role of ER stress and autophagy in AGEs-induced mesangial cell death is still unclear. Here, we investigated the effect and mechanism of AGEs on glomerular mesangial cells. AGEs dose-dependently decreased mesangial cell viability and induced cell apoptosis...
September 26, 2016: Scientific Reports
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