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https://www.readbyqxmd.com/read/29149599/autophagosomal-content-profiling-reveals-an-lc3c-dependent-piecemeal-mitophagy-pathway
#1
François Le Guerroué, Franziska Eck, Jennifer Jung, Tatjana Starzetz, Michel Mittelbronn, Manuel Kaulich, Christian Behrends
Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149494/inhibiting-mt2-tfe3-dependent-autophagy-enhances-melatonin-induced-apoptosis-in-tongue-squamous-cell-carcinoma
#2
Tengfei Fan, Huifeng Pi, Min Li, Zhenhu Ren, Zhijing He, Feiya Zhu, Li Tian, Manyu Tu, Jia Xie, Mengyu Liu, Yuming Li, Miduo Tan, Gaoming Li, Weijia Qing, Russel J Reiter, Zhengping Yu, Hanjiang Wu, Zhou Zhou
Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anti-carcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29148068/gastrodin-protects-myocardial-cells-against-hypoxia-reoxygenation-injury-in-neonatal-rats-by-inhibiting-cell-autophagy-through-the-activation-of-mtor-signals-in-pi3k-akt-pathway
#3
Xiang Li, Qinhui Zhu, Yuanyuan Liu, Zhiyong Yang, Bin Li
OBJECTIVES: This study aimed to investigate the protective effect of gastrodin (GAS) on myocardial cells with hypoxia/reoxygenation (H/R) injury in neonatal rats and explore the underlying mechanism. METHODS: Myocardial cells were extracted from neonatal rats and divided into six groups: control, H/R, H/R + Low-Concentration GAS, H/R + Middle-Concentration GAS, H/R + High-Concentration GAS and H/R + High-Concentration GAS + AKT Inhibitor groups. After 48-h treatment, cell viability, autophagosome quantity and the expression levels of LC3-II, p62, Akt, pAkt, mammalian target of rapamycin (mTOR) and uncoordinated 51-like kinase 1 (ULK1) in myocardial cells were made comparisons among each group...
November 17, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#4
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29147513/sortase-mediated-chemical-protein-synthesis-reveals-the-bidentate-binding-of-bisphosphorylated-p62-with-k63-diubiquitin
#5
Xiang-Long Tan, Man Pan, Yong Zheng, Shuai Gao, Lu-Jun Liang, Yi-Ming Li
Phosphorylation of S403 or S407 of the autophagic receptor protein p62 has recently been discovered to enhance the binding of p62 with ubiquitinated protein substrates to upregulate selective autophagy. To elucidate the molecular mechanism of how phosphorylation regulates the recruitment of ubiquitinated proteins, we report the first chemical synthesis of homogeneously phosphorylated p62, which enables the setting up of accurate in vitro systems for biochemical studies. Our synthesis employs the technology of sortase A-mediated protein hydrazide ligation, which successfully affords three types of phosphorylated p62 at the multi-milligram scale...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147488/the-downregulation-of-atg4b-mediated-by-microrna-34a-34c-5p-suppresses-rapamycin-induced-autophagy
#6
Yaran Wu, Xufang Dai, Zhenhong Ni, Xiaojing Yan, Fengtian He, Jiqin Lian
Objectives: Autophagy-related 4B (ATG4B) plays an important role in the process of autophagy induction. However, the molecular events that govern the expression of ATG4B in this process are not well known. Materials and Methods: Human ATG4B 3'-UTR region (1377 nt) containing miR-34a/miR-34c-5p binding site was amplified by PCR. Luciferase assay was used to assess the activity of reporter genes. Real-time PCR was used to detect the levels of miR-34a and miR-34c-5p...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29146903/wiskott-aldrich-syndrome-protein-regulates-autophagy-and-inflammasome-activity-in-innate-immune-cells
#7
Pamela P Lee, Damián Lobato-Márquez, Nayani Pramanik, Andrea Sirianni, Vanessa Daza-Cajigal, Elizabeth Rivers, Alessia Cavazza, Gerben Bouma, Dale Moulding, Kjell Hultenby, Lisa S Westerberg, Michael Hollinshead, Yu-Lung Lau, Siobhan O Burns, Serge Mostowy, Mona Bajaj-Elliott, Adrian J Thrasher
Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott-Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation is enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146131/dysregulation-of-autophagy-in-melanocytes-contributes-to-hypopigmented-macules-in-tuberous-sclerosis-complex
#8
Fei Yang, Lingli Yang, Mari Wataya-Kaneda, Junya Hasegawa, Tamotsu Yoshimori, Atsushi Tanemura, Daisuke Tsuruta, Ichiro Katayama
BACKGROUND: Tuberous sclerosis complex (TSC) gene mutations lead to constitutive activation of the mammalian target of rapamycin (mTOR) pathway, resulting in a broad range of symptoms. Hypopigmented macules are the earliest sign. Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood. OBJECTIVE: Recently emerging evidence supports a role for autophagy in skin pigmentation...
November 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29145153/the-pro-apoptosis-effect-of-sinomenine-in-renal-carcinoma-via-inducing-autophagy-through-inactivating-pi3k-akt-mtor-pathway
#9
Fei Deng, Yue-Xian Ma, Liang Liang, Ping Zhang, Jing Feng
Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29143455/understanding-the-functional-role-of-microrna-214-3p-in-atherosclerosis-for-the-identification-of-novel-targeted-therapies-to-prevent-or-reverse-endothelial-cell-dysfunction-and-stimulate-autophagy
#10
EDITORIAL
Adriana Georgescu
The original article by Jing Wang and collaborators, entitled "MicroRNA-214-3p: A Link between Autophagy and Endothelial Cell Dysfunction in Atherosclerosis", brings new data concerning molecular mechanisms linking decreased autophagy to endothelial dysfunction in atherosclerosis. In this issue of Acta Physiologica, the authors concluded that microRNA-214-3p (miR-214-3p) controls oxidized low-density lipoprotein (ox-LDL)-induced autophagy in human umbilical vein endothelial cells (HUVECs) by regulating intracellular levels of autophagy-related protein 5 (ATG5), and may have a relevant role in the pathogenesis of atherosclerosis...
November 16, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29142609/role-of-5-aza-cdr-in-mitomycin-c-chemosensitivity-of-t24-bladder-cancer-cells
#11
Hui-Hui Zhang, Bo Huang, You-Han Cao, Qing Li, Han-Feng Xu
Chemotherapeutic insensitivity is one of key obstacles to effectively treating muscle invasive bladder cancer. 5-Aza-2'-deoxycytidine (5-Aza-CdR) has been identified as a tumor suppressive agent in various types of cancer. The aim of the present study was to identify the effects of 5-Aza-CdR on the mitomycin-C (MMC) chemosensitivity of T24 bladder cancer cells and investigate the underlying mechanisms. T24 cells were treated with a combination of MMC and 5-Aza-CdR at various concentrations. The rates of proliferation and apoptosis were assessed by an MTT assay and flow cytometry, respectively...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29141547/cardioprotective-effects-of-serca2a-overexpression-against-ischemia-reperfusion-induced-injuries-in-rats
#12
Yan Jian, Li-Li Tian, Lin-Hui Wang, Xiao-Dong Zhao, Jing-Wei Chen, Koji Murao, Wei Zhu, Liang Dong, Guo-Qing Wang, Wan-Ping Sun, Guo-Xing Zhang
AIMS: The aim of the present study is to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after ischemia/reperfusion (I/R) exposure and the related mechanisms involved. METHODS AND RESULTS: Rats were subjected to left anterior descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats (Serca2aTG) rats compared to wild type (WT) rats...
November 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29141243/trolline-ameliorates-liver-fibrosis-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway-promoting-hsc-apoptosis-and-suppressing-autophagy
#13
Facheng Bai, Quanfang Huang, Jinlan Nie, Shengjuan Lu, Chunyuan Lu, Xunshuai Zhu, Yuxin Wang, Lang Zhuo, Zhongpeng Lu, Xing Lin
BACKGROUND/AIMS: Previous studies have shown that trolline possesses various forms of pharmacological activity, including antibacterial and antiviral potency. The present paper addressed the putative hepatoprotective effects of trolline. METHODS: Rats received 2 ml/kg CCl4 (mixed 1: 1 in peanut oil) intragastrically twice a week for 8 weeks to induce hepatic fibrosis. The animals were then treated with trolline for additional 4 weeks. Liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29138833/mir-16-mimics-inhibit-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-via-activation-of-autophagy-in-non-small-cell-lung-carcinoma-cells
#14
Hui Wang, Ying Zhang, Qian Wu, Yong-Bin Wang, Wei Wang
Autophagy is critical for the metastasis of cancer cells through induction of epithelial-to-mesenchymal transition (EMT). Activation of TGF-β signaling plays a key role in regulating autophagy. miR-16 may be associated with non-small cell lung carcinoma (NSCLC) progression. However, the role of miR-16 in NSCLC cell autophagy in the presence of TGF-β and the underlying mechanism are still unclear. To test whether miR-16 targets ATG3 which is involved in autophagy of NSCLC cells, we studied the expression levels of miR-16 and ATG3 in NSCLC patients, verified the targeting of ATG3 by miR-16 by luciferase reporter gene system, and investigated the role of miR-16 in the autophagy of NSCLC cells...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138806/effect-of-bis-hydroxymethyl-alkanoate-curcuminoid-derivative-mth-3-on-cell-cycle-arrest-apoptotic-and-autophagic-pathway-in-triple-negative-breast-adenocarcinoma-mda-mb-231-cells-an-in-vitro-study
#15
Ling-Chu Chang, Min-Tsang Hsieh, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Je-Wei Tsao, Yu-Jen Chiu, Sheng-Chu Kuo, Kuo-Hsiung Lee
Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells...
November 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29136784/the-alternation-of-autophagy-apoptosis-in-cd4-cd25-foxp3-tregs-on-the-developmental-stages-of-atherosclerosis
#16
Yuling Tian, Xiao Liang, Yue Wu
Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135079/cigarette-smoke-extract-and-isoprene-resulted-in-the-induction-of-apoptosis-and-autophagy-in-human-placenta-choriocarcinoma-jeg-3-cells
#17
Hae-Miru Lee, Kyung-Chul Choi
In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 μM) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29128638/ulk1-regulated-autophagy-a-mechanism-in-cellular-protection-for-aldh2-against-hyperglycemia
#18
Min Liu, Songhe Lu, Wei He, Le Zhang, Ying Ma, Ping Lv, Meijuan Ma, Wenjun Yu, Jiaxing Wang, Mingming Zhang, Yingmei Zhang, Yan Li
Mitochondrial aldehyde dehydrogenase 2 (ALDH2), an important enzyme in the elimination of toxic aldehydes, is involved in cardioprotection against diabetes mellitus. This study was designed to examine the mechanism behind ALDH2-offered protection against high glucose exposure with a focus on autophagy. H9C2 cells were cultured with normal or high glucose medium in the presence or absence of the ALDH2 agonist Alda-1. GFP-LC3 puncta and immunofluorescence were employed to assess autophagosome formation. Western blotting was applied to evaluate autophagy protein markers Atg5, LC3, p62, ULK1 phosphorylation and ALDH2...
November 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29128363/gbp3-promotes-glioma-cell-proliferation-via-sqstm1-erk1-2-axis
#19
Hui Xu, Lili Sun, Yanwen Zheng, Shuye Yu, Ou-Yang Jia, Hui Han, Xinliang Dai, Xiaoting Yu, Ming Li, Qing Lan
Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell-autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2)...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29128104/effects-of-intermedin-on-autophagy-in-cerebral-ischemia-reperfusion-injury
#20
Meng Wang, Jing Wang, Zhengang Liu, Xin Guo, Ning Wang, Nana Jia, Yanshu Zhang, Jie Yuan
OBJECTIVE: This study aimed to evaluate the effects of intermedin (IMD) on autophagy in cerebral ischemia/reperfusion (I/R) injury (CIRI). METHODS: Sixty rats were randomly averaged into four groups: sham, ischemia/reperfusion (I/R), IMD, and 3-methyladenine (3-MA). In the sham group, the right common carotid artery, external carotid artery, and internal carotid artery were detached, and no monofilament was inserted. In the other groups, two hours after cerebral ischemia, the rats were injected through the lateral ventricle with normal saline for I/R group, IMD for the IMD group, and 3-MA for the 3-MA group for 24h...
November 8, 2017: Neuropeptides
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