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https://www.readbyqxmd.com/read/28733114/targeting-heat-shock-factor-1-as-an-antiviral-strategy-against-dengue-virus-replication-in-vitro-and-in-vivo
#1
Tsung-Ting Tsai, Chia-Ling Chen, Cheng-Chieh Tsai, Chiou-Feng Lin
Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca(2+) and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes...
July 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28731223/neferine-modulates-igf-1r-nrf2-signaling-in-doxorubicin-treated-h9c2-cardiomyoblasts
#2
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7 and LC3B...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#3
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28728293/-curcumin-induces-apoptosis-and-protective-autophagy-in-human-gastric-cancer-cells-with-different-degree-of-differentiation
#4
W Li, Y Zhou, J Yang, H H Zhang, S L Zhao, T Zhang, J Huo, P Zheng
Objective: To investigate the effect of curcumin on the apoptosis and autophagy of human gastric cancer cells with different degree of differentiation. Methods: Gastric cancer cell lines BGC-823 and MKN-28 were treated with curcumin at different concentrations. The effect of curcumin on cell proliferation was measured by MTT assay. Apoptosis was assessed by flow cytometry. Autophagy status was analyzed by acridine orange staining. The expression levels of apoptotic and autophagy-related proteins were detected by Western blot...
July 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28722539/an-autophagy-driven-pathway-of-atp-secretion-supports-the-aggressive-phenotype-of-braf-v600e-inhibitor-resistant-metastatic-melanoma-cells
#5
Shaun Martin, Aleksandra M Dudek-Peric, Abhishek D Garg, Heleen Roose, Seyma Demirsoy, Sofie Van Eygen, Freya Mertens, Peter Vangheluwe, Hugo Vankelecom, Patrizia Agostinis
The ingrained capacity of melanoma cells to rapidly evolve towards an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28722508/atg5-and-atg7-dependent-autophagy-in-dopaminergic-neurons-regulates-cellular-and-behavioral-responses-to-morphine
#6
Ling-Yan Su, Rongcan Luo, Qianjin Liu, Jing-Ran Su, Lu-Xiu Yang, Yu-Qiang Ding, Lin Xu, Yong-Gang Yao
The molecular basis of chronic morphine exposure remains unknown. In this study, we hypothesized that macroautophagy/autophagy of dopaminergic neurons would mediate the alterations of neuronal dendritic morphology and behavioral responses induced by morphine. Chronic morphine exposure caused Atg5 (autophagy related 5)- and Atg7 (autophagy related 7)-dependent and dopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors. In cultured primary midbrain neurons, morphine treatment significantly reduced total dendritic length and complexity, and this effect could be reversed by knockdown of Atg5 or Atg7...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28716053/ibrutinib-a-bruton-s-tyrosine-kinase-inhibitor-exhibits-antitumoral-activity-and-induces-autophagy-in-glioblastoma
#7
Jin Wang, Xiaoyang Liu, Yongzhi Hong, Songtao Wang, Pin Chen, Aihua Gu, Xiaoyuan Guo, Peng Zhao
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers. In this study, we aimed to determine the role of ibrutinib on GBM. METHODS: Cell proliferation was determined by using cell viability, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and cell apoptosis were analyzed by flow cytometry...
July 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28703808/rip3-attenuates-the-pancreatic-damage-induced-by-deletion-of-atg7
#8
Xiaodong Zhou, Li Xie, Leizhou Xia, Frank Bergmann, Markus W Büchler, Guido Kroemer, Thilo Hackert, Franco Fortunato
Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703806/inhibition-of-autophagy-as-a-treatment-strategy-for-p53-wild-type-acute-myeloid-leukemia
#9
Hendrik Folkerts, Susan Hilgendorf, Albertus T J Wierenga, Jennifer Jaques, André B Mulder, Paul J Coffer, Jan Jacob Schuringa, Edo Vellenga
Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53(mut)), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53(R273H)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28700649/autophagy-mediates-cell-cycle-response-by-regulating-nucleocytoplasmic-transport-of-pax6-in-limbal-stem-cells-under-ultraviolet-a-stress
#10
Maria Laggner, Andreas Pollreisz, Gerald Schmidinger, Ursula Schmidt-Erfurth, Ying-Ting Chen
Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28699918/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#11
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696297/mtorc1-activates-srebp-2-by-suppressing-cholesterol-trafficking-to-lysosomes-in-mammalian-cells
#12
Walaa Eid, Kristin Dauner, Kevin C Courtney, AnneMarie Gagnon, Robin J Parks, Alexander Sorisky, Xiaohui Zha
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28696138/adipoq-adiponectin-induces-cytotoxic-autophagy-in-breast-cancer-cells-through-stk11-lkb1-mediated-activation-of-the-ampk-ulk1-axis
#13
Seung J Chung, Ganji Purnachandra Nagaraju, Arumugam Nagalingam, Nethaji Muniraj, Panjamurthy Kuppusamy, Alyssa Walker, Juhyung Woo, Balázs Győrffy, Ed Gabrielson, Neeraj K Saxena, Dipali Sharma
ADIPOQ/adiponectin, an adipocytokine secreted by adipocytes in the breast tumor microenvironment, negatively regulates cancer cell growth hence increased levels of ADIPOQ/adiponectin are associated with decreased breast cancer growth. However, its mechanisms of action remain largely elusive. We report that ADIPOQ/adiponectin induces a robust accumulation of autophagosomes, increases MAP1LC3B-II/LC3B-II and decreases SQSTM1/p62 in breast cancer cells. ADIPOQ/adiponectin-treated cells and xenografts exhibit increased expression of autophagy-related proteins...
July 11, 2017: Autophagy
https://www.readbyqxmd.com/read/28691995/the-role-of-psychological-stress-on-heart-autophagy-in-mice-with-heart-failure
#14
Xiao-Ting Lu, Xiao-Qiong Liu, Bo Wang, Yuan-Yuan Sun, Rui-Xue Yang, Yi-Fan Xing, Ping Sun, Ying-Bin Wang, Yu-Xia Zhao
OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. RESULTS: A one-week stress exposure significantly increased serum levels of corticosterone and Ang II (P= .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (P =...
July 7, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28685385/exclusive-activation-of-caspase-3-in-mossy-fibers-and-altered-dynamics-of-autophagy-markers-in-the-mice-hippocampus-upon-status-epilepticus-induced-by-kainic-acid
#15
A Rami, A Benz
Epileptic seizures are generally associated with pathological changes in the hippocampus such as astrogliosis, mossy fiber sprouting, and neuronal damage. However, more than 30% of temporal lobe epilepsy in humans shows neither neuronal damage nor mossy fiber sprouting despite chronic epileptic seizures. A similar situation exists in certain commonly used strains of mice, specifically C57BL/6 and BALB/c, which exhibit epileptic seizures, but no neuronal damage upon kainic acid administration. This suggests that intrinsic factors may influence the pathological manifestations of epilepsy...
July 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#16
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28678742/chronic-myeloid-leukemia-progenitor-cells-require-autophagy-when-leaving-hypoxia-induced-quiescence
#17
Angela Ianniciello, Amélie Guitart, Pierre-Yves Dumas, Claire Drullion, 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...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28677782/nicd-inhibits-cell-proliferation-and-promotes-apoptosis-and-autophagy-in-pc12-cells
#18
Bo Li, Ping Duan, Xuefei Han, Wenhai Yan, Ying Xing
Pheochromocytoma is a tumor of the adrenal medulla for which surgical resection is the only therapy. Though the Notch1 signaling pathway has been suggested as a target for pheochromocytoma treatment, the effect of Notch1 intracellular domain (NICD) on pheochromocytoma cell growth remains unknown. In the present study, the effect of NICD on pheochromocytoma cell growth was examined, by use of a tetracycline‑inducible system for NICD overexpression in the PC12 pheochromocytoma cell line. Flow cytometry was used to determine the effect of NICD on cell cycle phase distribution and apoptosis in PC12 cells...
June 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28667916/mir-210-facilitates-ecm-degradation-by-suppressing-autophagy-via-silencing-of-atg7-in-human-degenerated-np-cells
#19
Cheng Wang, Zi-Zhen Zhang, Wei Yang, Zhi-Hua Ouyang, Jing-Bo Xue, Xue-Lin Li, Jian Zhang, Wen-Kang Chen, Yi-Guo Yan, Wen-Jun Wang
Intervertebral disc degeneration (IDD) is thought to be the most common cause of low back pain. Dysregulation of microRNAs (miRNAs) is involved in the development of IDD. The aim of this study was to explore the influence of miR-210 on type II collagen (Col II) and aggrecan expression and possible mechanisms in human degenerated nucleus pulposus (NP) cells. Our results showed that miR-210 levels were significantly increased in degenerated NP tissues compared with healthy controls, and positively correlated with disc degeneration grade...
June 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28665330/effects-of-epigallocatechin-3-gallate-on-autophagic-lipolysis-in-adipocytes
#20
Sang-Nam Kim, Hyun-Jung Kwon, Seun Akindehin, Hyun Woo Jeong, Yun-Hee Lee
Previous studies demonstrated effects of green tea on weight loss; however, green tea-induced modulation of adipocyte function is not fully understood. Here, we investigated effects of the major green tea phytochemical, epigallocatechin-3-gallate (EGCG) on triglyceride contents, lipolysis, mitochondrial function, and autophagy, in adipocytes differentiated from C₃H10T1/2 cells and immortalized pre-adipocytes in vitro. EGCG reduced the triglycerol content significantly in adipocytes by 25%, comparable to the nutrient starvation state...
June 30, 2017: Nutrients
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