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https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#1
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28207432/spontaneous-canalicular-plug-erosion-after-punctal-plug-placement
#2
Xinxin Zhang, Maya Bitar, Richard M Davis
PURPOSE: To describe a case of keratoconjunctivitis sicca treated with punctal plug placement with the first reported complication of subsequent plug erosion through the canaliculus and extrusion through the lid. METHODS: Punctal plugs were placed in a patient with Sjogren syndrome for treatment of keratoconjunctivitis sicca. More than 12 years later, the plug was noted to have eroded through the canaliculus and extruded through the conjunctiva and lid. RESULTS: The extruded plug was removed, and punctal cautery was performed on 2 other puncta with improved symptom control...
February 15, 2017: Cornea
https://www.readbyqxmd.com/read/28169314/loss-of-hsulf-1-the-missing-link-between-autophagy-and-lipid-droplets-in-ovarian-cancer
#3
Debarshi Roy, Susmita Mondal, Ashwani Khurana, Deok-Beom Jung, Robert Hoffmann, Xiaoping He, Eleftheria Kalogera, Thomas Dierks, Edward Hammond, Keith Dredge, Viji Shridhar
Defective autophagy and deranged metabolic pathways are common in cancer; pharmacologic targeting of these two pathways could provide a viable therapeutic option. However, how these pathways are regulated by limited availability of growth factors is still unknown. Our study shows that HSulf-1 (endosulfatase), a known tumor suppressor which attenuates heparin sulfate binding growth factor signaling, also regulates interplay between autophagy and lipogenesis. Silencing of HSulf-1 in OV202 and TOV2223 cells (ovarian cancer cell lines) resulted in increased lipid droplets (LDs), reduced autophagic vacuoles (AVs) and less LC3B puncta...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157489/cathepsin-h-mediated-degradation-of-hdac4-for-matrix-metalloproteinase-expression-in-hepatic-stellate-cells-implications-of-epigenetic-suppression-of-matrix-metalloproteinases-in-fibrosis-through-stabilization-of-class-iia-histone-deacetylases
#4
Zemin Yang, Yu Liu, Lan Qin, Pengfei Wu, Zanxian Xia, Mei Luo, Yilan Zheng, Hidekazu Tsukamoto, Zongyun Ju, Danmei Su, Han Kang, Zhixiong Xiao, Sujun Zheng, Zhongping Duan, Richard Hu, Qiang Wang, Stephen J Pandol, Yuan-Ping Han
In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts)...
January 31, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28154825/bu-zhong-yi-qi-decoction-the-water-extract-of-chinese-traditional-herbal-medicine-enhances-cisplatin-cytotoxicity-in-a549-ddp-cells-through-induction-of-apoptosis-and-autophagy
#5
Ning Yu, Ying Xiong, Chun Wang
Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28153718/hadha-the-alpha-subunit-of-the-mitochondrial-trifunctional-protein-is-involved-in-long-chain-fatty-acid-induced-autophagy-in-intestinal-epithelial-cells
#6
Chiaki Maeyashiki, Shigeru Oshima, Kana Otsubo, Masanori Kobayashi, Yoichi Nibe, Yu Matsuzawa, Michio Onizawa, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe
Genome-wide association studies have identified autophagy-related susceptibility genes for inflammatory bowel disease (IBD); however, whether autophagy regulators can be utilized as therapeutic targets remains unclear. To identify novel microtubule-associated protein 1 light chain 3 (LC3)-interacting proteins in intestinal epithelial cells (IECs), we isolated primary IECs from green fluorescent protein (GFP)-LC3 mice. We performed immunoprecipitation with a GFP antibody and then analyzed co-immunoprecipitates by mass spectrometry...
January 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28151484/berbamine-postconditioning-protects-the-heart-from-ischemia-reperfusion-injury-through-modulation-of-autophagy
#7
Yanjun Zheng, Shanshan Gu, Xuxia Li, Jiliang Tan, Shenyan Liu, Yukun Jiang, Caimei Zhang, Ling Gao, Huang-Tian Yang
Pretreatment of berbamine protects the heart from ischemia/reperfusion (I/R) injury. However it is unknown whether it has cardioprotection when given at the onset of reperfusion (postconditioning (PoC)), a protocol with more clinical impact. Autophagy is upregulated in I/R myocardium and exacerbates cardiomyocyte death during reperfusion. However, it is unknown whether the autophagy during reperfusion is regulated by berbamine. Here we investigated whether berbamine PoC (BMPoC) protects the heart through regulation of autophagy by analyzing the effects of BMPoC on infarct size and/or cell death, functional recovery and autophagy in perfused rat hearts and isolated cardiomyocytes subjected to I/R...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28143984/in-situ-tagged-nsp15-reveals-interactions-with-coronavirus-replication-transcription-complex-associated-proteins
#8
Jeremiah Athmer, Anthony R Fehr, Matthew Grunewald, Everett Clinton Smith, Mark R Denison, Stanley Perlman
: Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28135713/microrna-141-targets-sirt1-and-inhibits-autophagy-to-reduce-hbv-replication
#9
Ying Yang, Yanning Liu, Jihua Xue, Zhenggang Yang, Yu Shi, Yixian Shi, Guohua Lou, Shanshan Wu, Jinjin Qi, Weixia Liu, Zhi Chen, Jing Wang
BACKGROUND/AIMS: About 400 million individuals are chronically infected with hepatitis B virus, at high risk of developing liver cirrhosis and hepatocellular carcinoma. Recent studies have demonstrated an interaction between hepatitis B virus replication and autophagy activity of hepatocytes. In the present study, we aimed to investigate the role of miR-141 in regulating autophagy and hepatitis B virus replication. METHODS: The expression of HBV-DNA, miR-141 and Sirt1 mRNA was determined by quantitative real-time PCR analysis...
January 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28131804/downregulation-of-autophagy-related-gene-atg5-and-gabarap-expression-by-ifn-%C3%AE-1-contributes-to-its-anti-hcv-activity-in-human-hepatoma-cells
#10
Xu Li, Yu Li, Shoucai Fang, Jinming Su, Junjun Jiang, Bingyu Liang, Jiegang Huang, Bo Zhou, Ning Zang, Wenzhe Ho, Jieliang Li, Yiping Li, Hui Chen, Li Ye, Hao Liang
Type-III interferon (IFN-λ), the most recently discovered family of IFNs, shares common features with type I IFNs, but also has many distinctive activities. It is not clear that whether IFN-λ has additional antiviral mechanisms. In this study, we investigated the effects of IFN-λ on autophagy, a cellular process closely related to hepatitis C virus (HCV) infection in human hepatoma Huh7 cells. Our results showed that IFN-λ1 treatment inhibit autophagic activity in Huh7 cells, as evidenced by the decreased expression of microtubule-associated protein 1 light chain 3B (LC3B)-II and conversion of LC3B-I to LC3B-II, decreased formation of GFP-LC3 puncta and accumulation of autophagosomes...
January 26, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28122914/localization-of-ndr2-to-peroxisomes-and-its-role-in-ciliogenesis
#11
Shoko Abe, Tomoaki Nagai, Moe Masukawa, Kanji Okumoto, Yuta Homma, Yukio Fujiki, Kensaku Mizuno
Nuclear Dbf2-related (NDR) kinases, comprising NDR1 and NDR2, are serine/threonine kinases that play crucial roles in the control of cell proliferation, apoptosis, and morphogenesis. We recently showed that NDR2, but not NDR1, is involved in primary cilium formation; however, the mechanism underlying their functional difference in ciliogenesis is unknown. To address this issue, we examined their subcellular localization. Despite their close sequence similarity, NDR2 exhibited punctate localization in the cytoplasm, whereas NDR1 was diffusely distributed within the cell...
January 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28122248/mdma-induced-neurotoxicity-of-serotonin-neurons-involves-autophagy-and-rilmenidine-is-protective-against-its-pathobiology
#12
Linda D Mercer, Gavin C Higgins, Chew L Lau, Andrew J Lawrence, Philip M Beart
Toxicity of 3,4-methylenedioxymethamphetamine (MDMA) towards biogenic amine neurons is well documented and in primate brain predominantly affects serotonin (5-HT) neurons. MDMA induces damage of 5-HT axons and nerve fibres and intracytoplasmic inclusions. Whilst its pathobiology involves mitochondrially-mediated oxidative stress, we hypothesised MDMA possessed the capacity to activate autophagy, a proteostatic mechanism for degradation of cellular debris. We established a culture of ventral pons from embryonic murine brain enriched in 5-HT neurons to explore mechanisms of MDMA neurotoxicity and recruitment of autophagy, and evaluated possible neuroprotective actions of the clinically approved agent rilmenidine...
January 22, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28105281/n-1-benzyl-3-5-dimethyl-1h-pyrazol-4-yl-benzamides-antiproliferative-activity-and-effects-on-mtorc1-and-autophagy
#13
Teng Ai, Rose Willett, Jessica Williams, Rui Ding, Daniel J Wilson, Jiashu Xie, Do-Hyung Kim, Rosa Puertollano, Liqiang Chen
Guided by antiproliferative activity in MIA PaCa-2 cells, we have performed preliminary structure-activity relationship studies on N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides. Two selected compounds showed submicromolar antiproliferative activity and good metabolic stability. Both compounds reduced mTORC1 activity and increased autophagy at the basal level. In addition, they disrupted autophagic flux by interfering with mTORC1 reactivation and clearance of LC3-II under starvation/refeed conditions, as evidenced by accumulation of LC3-II and abnormal LC3 labeled punctae...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28103582/ampk-autophagy-inhibition-sensitizes-icaritin-induced-anti-colorectal-cancer-cell-activity
#14
Chunxian Zhou, Jun Gu, Gang Zhang, Da Dong, Qunying Yang, Min-Bin Chen, Dongfeng Xu
The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28100648/multi-scale-structural-analysis-of-plant-er-pm-contact-sites
#15
Heather E McFarlane, Eun Kyoung Lee, Laura S van Bezouwen, Bradford Ross, Abel Rosado, A Lacey Samuels
Membrane contact sites (MCS) are recognized across eukaryotic systems as important nanostructures. Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCS) are involved in excitation-contraction coupling, signalling, and plant responses to stress. In this report, we perform a multi-scale structural analysis of Arabidopsis EPCS that combine live cell imaging, quantitative transmission electron microscopy (TEM), and electron tomography over a developmental gradient. To place EPCS in the context of the entire cortical ER, we examined GFP-HDEL in living cells over a developmental gradient, then SYT1-GFP was used as a specific marker of EPCS...
January 18, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28097654/melanopsin-expressing-ganglion-cells-in-human-retina-morphology-distribution-and-synaptic-connections
#16
Subha Nasir-Ahmad, Sammy C S Lee, Paul R Martin, Ulrike Grünert
Melanopsin-expressing retinal ganglion cells are intrinsically photosensitive cells that are involved in non-image forming visual processes such as the pupillary light reflex and circadian entrainment but also contribute to visual perception. Here we used immunohistochemistry to study the morphology, density, distribution and synaptic connectivity of melanopsin-expressing ganglion cells in four post mortem human donor retinas. Two types of melanopsin-expressing ganglion cells were distinguished based on their dendritic stratification near either the outer or the inner border of the inner plexiform layer...
January 18, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28095639/early-involvement-of-lysosome-dysfunction-in-the-degeneration-of-cerebral-cortical-neurons-caused-by-the-lipid-peroxidation-product-4-hydroxynonenal
#17
Shi Zhang, Erez Eitan, Mark P Mattson
Free radical-mediated oxidative damage to proteins, lipids and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy - lysosome pathway in rat primary cortical neurons...
January 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28077712/changes-in-properties-of-auditory-nerve-synapses-following-conductive-hearing-loss
#18
Xiaowen Zhuang, Wei Sun, Matthew A Xu-Friedman
: Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077445/human-antiviral-protein-ifix-suppresses-viral-gene-expression-during-hsv-1-infection-and-is-counteracted-by-virus-induced-proteasomal-degradation
#19
Marni S Crow, Ileana M Cristea
The interferon inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes antiviral cytokines expression. How IFIX exerts its host defense functions and whether it is inhibited by the virus remains unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection...
January 11, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28077330/dehydropachymic-acid-decreases-bafilomycin-a1-induced-%C3%AE-amyloid-accumulation-in-pc12-cells
#20
Mengyao Yu, Xiaoyan Xu, Nan Jiang, Wei Wei, Fang Li, Liming He, Xia Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Fuling, the sclerotium of Poria cocos, was frequently used in traditional Chinese medicine (TCM) formulae for Alzheimer's disease (AD) intervention over the past 10 centuries. And its extracts exhibited significant effects in both cellular and animal models of AD in previous studies. However, its mechanisms on prevention and treatment of AD have not been well elucidated yet. AIM OF THE STUDY: To investigate the effect and corresponding mechanisms of dehydropachymic acid, which is one of the major triterpenes in Poria cocos, on the clearance of β-Amyloid accumulation in bafilomycin A1 induced PC12 cells...
January 7, 2017: Journal of Ethnopharmacology
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