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Kun Ma, Haoyu Wu, Peng Li, Baixiang Li
Atrazine (2-chloro-4-ethylamino-6-isopropylamine-1,3,5-triazine; ATR) has been demonstrated to regulate autophagy- and apoptosis-related proteins in doparminergic neuronal damage. In our study, we investigated the role of LC3-II in ATR-induced degeneration of dopaminergic neurons. In vivo dopaminergic neuron degeneration model was set up with ATR treatment and confirmed by the behavioral responses and pathological analysis. Dopaminergic neuron cells were transfected with LC3-II siRNA and treated with ATR to observe cell survival and reactive oxygen species release...
August 2, 2018: Acta Biochimica et Biophysica Sinica
Chiao-Chun Liao, Ming-Yi Ho, Shu-Mei Liang, Chi-Ming Liang
The relationship between macroautophagy/autophagy and miRNA in regulating cancer cell motility is not clearly delineated. Here, we found that induction of BECN1-dependent or -independent autophagy decreased ubiquitin-binding proteins SQSTM1/p62 and CALCOCO2/NDP52. Downregulation of SQSTM1 (but not CALCOCO2) led to a decrease of the miRNA-processing enzyme DICER1 and the miRNA effector AGO2. The autophagy-mediated reduction of levels of SQSTM1, DICER1 or AGO2 resulted in increased MIRLET7A-3P (but not MIRLET7A-5P or PRE-MIRLET7A miRNA) and suppressed ovarian cancer motility...
August 6, 2018: Autophagy
Alexa Parousis, Heather N Carter, Claudia Tran, Avigail T Erlich, Zahra S Mesbah Moosavi, Marion Pauly, David A Hood
Macroautophagy/autophagy is a survival mechanism that facilitates protein turnover in post-mitotic cells in a lysosomal-dependent process. Mitophagy is a selective form of autophagy, which arbitrates the selective recognition and targeting of aberrant mitochondria for degradation. Mitochondrial content in cells is the net balance of mitochondrial catabolism via mitophagy, and organelle biogenesis. Although the latter process has been well described, mitophagy in skeletal muscle is less understood, and it is currently unknown how these two opposing mechanisms converge during contractile activity...
August 4, 2018: Autophagy
Ivone Leong
In the original version of the published article, the reference was incorrect. The reference should have read 'Huang, J. et al. Adipocyte p62/SQSTM1 suppresses tumorigenesis through opposite regulations of metabolism in adipose tissue and tumour. Cancer Cell 33, 770-784. This has now been corrected in the HTML and PDF version of the article.
August 2, 2018: Nature Reviews. Endocrinology
R Alessia Battista, Massimo Resnati, Cecilia Facchi, Elena Ruggieri, Floriana Cremasco, Francesca Paradiso, Ugo Orfanelli, Leone Giordano, Mario Bussi, Simone Cenci, Enrico Milan
To cope with intrinsic and environmental stress, cancer cells rely on adaptive pathways more than non-transformed counterparts. Such non-oncogene addiction offers new therapeutic targets and strategies to overcome chemoresistance. In an attempt to study the role of adaptive pathways in acquired drug resistance in carcinoma cells, we devised a model of in vitro conditioning to three standard chemotherapeutic agents, cisplatin, 5-fluorouracil, and docetaxel, from the epithelial cancer cell line, HEp-2, and investigated the mechanisms underlying reduced drug sensitivity...
2018: PloS One
Xiaobing Zhang, Yunfei Song, Yipei Ding, Wei Wang, Ling Liao, Jin Zhong, Pengbo Sun, Fan Lei, Yaou Zhang, Weidong Xie
Obesity and nonalcoholic fatty liver disease (NAFLD) are highly prevalent and cause numerous metabolic diseases. However, drugs for the prevention and treatment of obesity and NAFLD remain unavailable. In this study, we investigated the effects of mogrosides (luo han guo, LH) in Siraitia grosvenorii saponins on high-fat-diet-induced obesity and NAFLD in mice. We found that compared with the negative control, LH reduced body and liver weight. LH also decreased fat accumulation and increased AMP-activated protein kinase (AMPK) phosphorylation (pAMPK) levels in mouse livers...
July 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Chi Zhou, Jin Huang, Qing Li, Chenao Zhan, Ying He, Jinyan Liu, Zheng Wen, Dao Wen Wang
BACKGROUND: Chronic drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, and cardiac fibrosis is a consequence of these alcoholic injuries. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids to less bioactive diols, and epoxyeicosatrienoic acids have cardioprotective properties. However, the effects of sEH inhibition in ethanol-induced cardiac fibrosis are unknown. METHODS AND RESULTS: This study was designed to investigate the role and underlying mechanisms of sEH inhibition in chronic ethanol feeding-induced cardiac fibrosis...
July 26, 2018: Alcoholism, Clinical and Experimental Research
Charleen T Chu
Over the past 20 years, the concept of mammalian autophagy as a nonselective degradation system has been repudiated, due in part to important discoveries in neurodegenerative diseases, which opened the field of selective autophagy. Protein aggregates and damaged mitochondria represent key pathological hallmarks shared by most neurodegenerative diseases. The landmark discovery in 2007 of p62/SQSTM1 as the first mammalian selective autophagy receptor defined a new family of autophagy-related proteins that serve to target protein aggregates, mitochondria, intracellular pathogens and other cargoes to the core autophagy machinery via an LC3-interacting region (LIR)-motif...
July 17, 2018: Neurobiology of Disease
Ruud H Wijdeven, Marvin M van Luijn, Annet F Wierenga-Wolf, Jimmy J Akkermans, Peter J van den Elsen, Rogier Q Hintzen, Jacques Neefjes
The cytokine interferon-γ (IFNγ) can induce expression of MHC class II (MHCII) on many different cell types, leading to antigen presentation to CD4+ T cells and immune activation. This has also been linked to anti-tumour immunity and graft-versus-host disease. The extent of MHCII upregulation by IFNγ is cell type-dependent and under extensive control of epigenetic regulators and signalling pathways. Here, we identify novel genetic and chemical factors that control this form of MHCII expression. Loss of the oxidative stress sensor Keap1, autophagy adaptor p62/SQSTM1, ubiquitin E3-ligase Cullin-3 and chromatin remodeller BPTF impair IFNγ-mediated MHCII expression...
July 18, 2018: EMBO Reports
Jian Yin, Ge Gong, Chao Sun, Zhaoyang Yin, Chao Zhu, Bin Wang, Qin Hu, Yuerong Zhu, Xinhui Liu
Angiogenesis plays a key role in the repair of large segmental bone defects with tissue-engineered bones. However, there is no effective method of promoting angiogenesis in tissue-engineered bone. Both angiopoietin 2 (Ang2) and autophagy have been shown to be involved in angiogenesis, but their roles in angiogenesis of tissue-engineered bone remains unknown. In this in vivo study, a radius bone defect was created in New Zealand white rabbits, which were then treated by implantation of a hydroxyapatite/collagen scaffold followed by injection of different concentrations of Ang2...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jakob Mejlvang, Hallvard Olsvik, Steingrim Svenning, Jack-Ansgar Bruun, Yakubu Princely Abudu, Kenneth Bowitz Larsen, Andreas Brech, Tom E Hansen, Hanne Brenne, Terkel Hansen, Harald Stenmark, Terje Johansen
It is not clear to what extent starvation-induced autophagy affects the proteome on a global scale and whether it is selective. In this study, we report based on quantitative proteomics that cells during the first 4 h of acute starvation elicit lysosomal degradation of up to 2-3% of the proteome. The most significant changes are caused by an immediate autophagic response elicited by shortage of amino acids but executed independently of mechanistic target of rapamycin and macroautophagy. Intriguingly, the autophagy receptors p62/SQSTM1, NBR1, TAX1BP1, NDP52, and NCOA4 are among the most efficiently degraded substrates...
July 17, 2018: Journal of Cell Biology
K Feidantsis, K Mellidis, E Galatou, Z Sinakos, A Lazou
BACKGROUND AND AIM: The association of diabetes mellitus (DM) and poor metabolic control with high incidence of cardiovascular diseases is well established. The aim of this study was to investigate the potential cardioprotective effect of crocin (Crocus sativus L. extract) on diabetic heart dysfunction and to elucidate the mediating molecular mechanisms. METHODS AND RESULTS: Streptozotocin (STZ)-induced diabetic rats were treated with two different concentrations of crocin (10 or 20 mg/kg), while isolated cardiac myocytes exposed to 25 mM glucose, were treated with 1 or 10 μM of crocin...
July 13, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Jun Lou, Yongli Wang, Ximing Zheng, Weiqiang Qiu
Autophagy is a crucial host-defense mechanism against Mycobacterium tuberculosis (Mtb) infection by spanning innate and adaptive immune functions. TRIM22 is a member of tripartite motif family protein which involved in innate immunity and autophagy process. However, its role in the modulation of bacterial infection has not been investigated. Here, we demonstrated that TRIM22 is upregulated in a dose-dependent and time-dependent manner during Mtb infection of THP-1 cells. Downregulation of TRIM22 significantly decreased light chain 3 (LC3)-II protein level and the formation of LC3 puncta, while it markedly increased SQSTM1, a marker of autophagic degradation, in Mtb-infected THP-1 cells...
July 16, 2018: Journal of Cellular Biochemistry
Jarish N Cohen, Iwei Yeh, Richard C Jordan, Rebecca J Wolsky, Andrew E Horvai, Timothy H McCalmont, Philip E LeBoit
Non-neural granular cell tumor (NNGCT; also known as primitive polypoid granular cell tumor) is a rare neoplasm composed of large ovoid cells with abundant granular cytoplasm, variable nuclear pleomorphism, and the potential for regional lymph node spread. In contrast to conventional granular cell tumor (GCT), NNGCT lacks S100 expression and can exhibit greater nuclear atypia and mitotic activity. Therefore, we investigated clinicopathologic features of 12 NNGCT, and also used next-generation sequencing to identify potential driver events in a subset of NNGCT and 6 GCT...
July 13, 2018: American Journal of Surgical Pathology
Arishya Sharma, Turkeya Alswillah, Kamini Singh, Payel Chatterjee, Belinda Willard, Monica Venere, Matthew K Summers, Alexandru Almasan
Recent reports have made important revelations, uncovering direct regulation of DNA damage response (DDR)-associated proteins and chromatin ubiquitination (Ubn) by macroautophagy/autophagy. Here, we report a previously unexplored connection between autophagy and DDR, via a deubiquitnase (DUB), USP14. Loss of autophagy in prostate cancer cells led to unrepaired DNA double-strand breaks (DSBs) as indicated by persistent ionizing radiation (IR)-induced foci (IRIF) formation for γH2AFX, and decreased protein levels and IRIF formation for RNF168, an E3-ubiquitin ligase essential for chromatin Ubn and recruitment of critical DDR effector proteins in response to DSBs, including TP53BP1...
July 11, 2018: Autophagy
Wenxia Xu, Qi Wei, Mengjiao Han, Bingluo Zhou, Hanying Wang, Jianbing Zhang, Qiang Wang, Jie Sun, Lifeng Feng, Shouyu Wang, Yang Ye, Xian Wang, Jianwei Zhou, Hongchuan Jin
Chemotherapy is one of the most important approaches for the treatment of various cancers. However, tumor cells often develop resistance to chemotherapeutic drugs. The tumor microenvironment reconstituted by various cytokines secreted from immune cells was recently found to play important roles in affecting therapeutic response of tumor cells. Herein, we reported that tumor cells can secrete autocrine cytokines to confer chemoresistance by inactivating proapoptotic autophagy. Through cytokine screening, we found that drug resistant cancer cells secreted more CCL2 than drug sensitive cells...
2018: International Journal of Biological Sciences
Yan Kang, Peiheng He, Hua Wang, Yibiao Ye, Xing Li, Peigen Xie, Bowen Wu
PURPOSE: Osteosarcoma is a common primary malignant bone tumour, and its cure rate has stagnated over the past 25-30 years. Brazilin, a purified natural product from sappan wood (Caesalpinia sappan L.), has been proved to possess potent anti-cancer effects. In this study, we investigated the anti-cancer effect of brazilin on human osteosarcoma and elucidated the underlying mechanisms. METHODS: We exposed MG-63 cells to different concentrations of brazilin (5, 10 and 20 µM) for 24 h...
July 9, 2018: Cancer Chemotherapy and Pharmacology
Sriganesh Ramachandra Rao, Bruce A Pfeffer, Néstor Más Gómez, Lara A Skelton, Ueda Keiko, Janet R Sparrow, Aryn M Rowsam, Claire H Mitchell, Steven J Fliesler
Treatment of rats with the cholesterol pathway inhibitor AY9944 produces an animal model of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive disease caused by defective cholesterol synthesis. This SLOS rat model undergoes progressive and irreversible degeneration of the neural retina, with associated pathological features of the retinal pigmented epithelium (RPE). Here, we provide further insights into the mechanism involved in the RPE pathology. In the SLOS rat model, markedly increased RPE apical autofluorescence is observed, compared to untreated animals, which correlates with increased levels of A2E and other bisretinoids...
July 31, 2018: Autophagy
Dae-Hee Lee, Daeho Kim, Sung Tae Kim, Soyeon Jeong, Jung Lim Kim, Sang Mi Shim, Ah Jung Heo, Xinxin Song, Zong Sheng Guo, David L Bartlett, Sang Cheul Oh, Junho Lee, Yoshiro Saito, Bo Yeon Kim, Yong Tae Kwon, Yong J Lee
Macroautophagy is induced under various stresses to remove cytotoxic materials, including misfolded proteins and their aggregates. These protein cargoes are collected by specific autophagic receptors such as SQSTM1/p62 (sequestosome 1) and delivered to phagophores for lysosomal degradation. To date, little is known about how cells sense and react to diverse stresses by inducing the activity of SQSTM1. Here, we show that the peroxiredoxin-like redox sensor PARK7/DJ-1 modulates the activity of SQSTM1 and the targeting of ubiquitin (Ub)-conjugated proteins to macroautophagy under oxidative stress caused by TNFSF10/TRAIL (tumor necrosis factor [ligand] superfamily, member 10)...
July 23, 2018: Autophagy
Annadurai Thangaraj, Palsamy Periyasamy, Ke Liao, Venkata Sunil Bendi, Shannon Callen, Gurudutt Pendyala, Shilpa Buch
While the advent of combination antiretroviral therapy (cART) has dramatically increased the life expectancy of HIV-1 infected individuals, paradoxically, however, the prevalence of HIV-1-associated neurocognitive disorders is on the rise. Based on the premise that the cytotoxic HIV-1 protein, transactivator of transcription (TAT), a known activator of glial cells that is found to persist in the central nervous system (CNS) despite cART, we sought to explore the role of defective mitophagy in HIV-1 TAT-mediated microglial activation...
July 26, 2018: Autophagy
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