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https://www.readbyqxmd.com/read/28437526/prominin-1-is-a-novel-regulator-of-autophagy-in-the-human-retinal-pigment-epithelium
#1
Sujoy Bhattacharya, Jinggang Yin, Christina S Winborn, Qiuhua Zhang, Junming Yue, Edward Chaum
Purpose: Prominin-1 (Prom1) is a transmembrane glycoprotein, which is expressed in stem cell lineages, and has recently been implicated in cancer stem cell survival. Mutations in the Prom1 gene have been shown to disrupt photoreceptor disk morphogenesis and cause an autosomal dominant form of Stargardt-like macular dystrophy (STGD4). Despite the apparent structural role of Prom1 in photoreceptors, its role in other cells of the retina is unknown. The purpose of this study is to investigate the role of Prom1 in the highly metabolically active cells of the retinal pigment epithelium (RPE)...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28433650/long-noncoding-rna-malat1-is-a-potent-autophagy-inducer-protecting-brain-microvascular-endothelial-cells-against-oxygen-glucose-deprivation-reoxygenation-induced-injure-by-sponing-mir-26b-and-upregulating-ulk2-expression
#2
Zhijun Li, Jing Li, Na Tang
Brain microvascular endothelial cell (BMEC) injury induced by ischemia-reperfusion (I/R) is the initial stage of blood-brain barrier (BBB) disruption, which results in a poor prognosis in ischemic stroke patients. Autophagy has been shown to have protective effects on BMECs against cerebral ischemic insults. However, molecular mechanism of BMEC autophagy during I/R is unclear. Long noncoding RNAs (lncRNAs) are emerging as new factors involved in cell autophagy. LncRNA Malat1 is one of the most highly upregulated I/R or OGD/R-responsive endothelial lncRNA and plays a protective role in BMECs against cerebral ischemic insults...
April 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#3
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28427888/dopamine-elevates-intracellular-zinc-concentration-in-cultured-rat-embryonic-cortical-neurons-through-the-camp-nitric-oxide-signaling-cascade
#4
Hui-Hsing Hung, Lung-Sen Kao, Pei-Shan Liu, Chien-Chang Huang, De-Ming Yang, Chien-Yuan Pan
Zinc ion (Zn(2+)), the second most abundant transition metal after iron in the body, is essential for neuronal activity and also induces toxicity if the concentration is abnormally high. Our previous results show that exposure of cultured cortical neurons to dopamine elevates intracellular Zn(2+) concentrations ([Zn(2+)]i) and induces autophagosome formation but the mechanism is not clear. In this study, we characterized the signaling pathway responsible for the dopamine-induced elevation of [Zn(2+)]i and the effect of [Zn(2+)]i in modulating the autophagy in cultured rat embryonic cortical neurons...
April 17, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28415949/%C3%AE-catenin-promotes-intracellular-bacterial-killing-via-suppression-of-pseudomonas-aeruginosa-triggered-macrophage-autophagy
#5
Qiang Fu, Kang Chen, Qian Zhu, Weijia Wang, Fuda Huang, Lishao Miao, Xinger Wu
Objective To investigate β-catenin-mediated bacterial elimination during Pseudomonas aeruginosa infection of macrophage-like RAW264.7 cells. Methods Cell viability and catenin beta 1 ( CTNNB1) expression in RAW264.7 cells following P. aeruginosa infection versus uninfected cells, were detected by cell counting kit-8 assay and β-catenin Western blots. RAW264.7 cells with CTNNB1 overexpression were established with β-catenin lentivirus using flow cytometry and clonogenic limiting dilution assays. Bacterial killing was measured by plate counts; phagocytosis and nitric oxide (NO) were measured by flow cytometry; and reactive oxygen species (ROS) were measured using Griess reaction...
April 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28413468/antitumor-effect-of-sunitinib-in-human-prostate-cancer-cells-functions-via-autophagy
#6
Bangqi Wang, Dongyuan Lu, Min Xuan, Weilie Hu
The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib in vitro. Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412648/content-decline-of-serca-inhibitors-saikosaponin-a-and-d-attenuates-cardiotoxicity-and-hepatotoxicity-of-vinegar-baked-radix-bupleuri
#7
Shifeng Wang, Yuxin Zhang, Qiao Zhang, Sha Peng, Chen Shen, Yangyang Yu, Minyu Zhang, Wei Yang, Qinghua Wu, Yanling Zhang, Shiyou Li, Yanjiang Qiao
Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger toxic responses on cardiomyocytes and hepatocytes than the other three saikosaponins in equivalent concentrations...
April 4, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#8
Betty Yuen Kwan Law, Flora Gordillo-Martínez, Yuan Qing Qu, Ni Zhang, Su Wei Xu, Paolo Saul Coghi, Simon Wing Fai Mok, Jianru Guo, Wei Zhang, Elaine Lai Han Leung, Xing Xing Fan, An Guo Wu, Wai Kit Chan, Xiao Jun Yao, Jing Rong Wang, Liang Liu, Vincent Kam Wai Wong
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394432/immunofluorescence-reveals-unusual-patterns-of-labelling-for-connexin43-localized-to-calbindin-d28k-positive-interstitial-cells-in-the-pineal-gland
#9
D D Tsao, S G Wang, B D Lynn, J I Nagy
Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 μm) or as unusually large pools of Cx43 ranging up to 4-7 μm in diameter or length...
April 10, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28386219/ncam-regulates-inhibition-and-excitability-in-layer-2-3-pyramidal-cells-of-anterior-cingulate-cortex
#10
Xuying Zhang, Chelsea S Sullivan, Megan B Kratz, Michael R Kasten, Patricia F Maness, Paul B Manis
The neural cell adhesion molecule (NCAM), has been shown to be an obligate regulator of synaptic stability and pruning during critical periods of cortical maturation. However, the functional consequences of NCAM deletion on the organization of inhibitory circuits in cortex are not known. In vesicular gamma-amino butyric acid (GABA) transporter (VGAT)-channelrhodopsin2 (ChR2)-enhanced yellow fluorescent protein (EYFP) transgenic mice, NCAM is expressed postnatally at perisomatic synaptic puncta of EYFP-labeled parvalbumin, somatostatin and calretinin-positive interneurons, and in the neuropil in the anterior cingulate cortex (ACC)...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28374157/chalcone-flavokawain-b-induces-autophagic-cell-death-via-reactive-oxygen-species-mediated-signaling-pathways-in-human-gastric-carcinoma-and-suppresses-tumor-growth-in-nude-mice
#11
Chia-Ting Chang, You-Cheng Hseu, Varadharajan Thiyagarajan, Kai-Yuan Lin, Tzong-Der Way, Mallikarjuna Korivi, Jiuun-Wang Liao, Hsin-Ling Yang
Flavokawain B (FKB), a naturally occurring chalcone in kava extracts, has been reported to possess anticancer activity. However, the effect of FKB on gastric cancer remains unclear. We examined the in vitro and in vivo anticancer activity and autophagy involvement of FKB and determined the underlying molecular mechanisms. FKB is potently cytotoxic to human gastric cancer cells (AGS/NCI-N87/KATO-III/TSGH9201) and mildly toxic towards normal (Hs738) cells and primary mouse hepatocytes. FKB-induced AGS cell death was characterized by autophagy, not apoptosis, as evidenced by increased LC3-II accumulation, GFP-LC3 puncta and acidic vesicular organelles (AVOs) formation, without resulting procaspase-3/PARP cleavage...
April 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28369910/acute-ethanol-exposure-induced-autophagy-mediated-cardiac-injury-via-activation-of-the-ros-jnk-bcl-2-pathway
#12
Zhongxin Zhu, Yewei Huang, Lingchun Lv, Youli Tao, Minglong Shao, Congcong Zhao, Mei Xue, Jia Sun, Chao Niu, Yang Wang, Sunam Kim, Weitao Cong, Wei Mao, Litai Jin
Binge drinking is associated with increased cardiac autophagy, and often triggers heart injury. Given the essential role of autophagy in various cardiac diseases, this study was designed to investigate the role of autophagy in ethanol-induced cardiac injury and the underlying mechanism. Our study showed that ethanol exposure enhanced the levels of LC3-II and LC3-II positive puncta and promoted cardiomyocyte apoptosis in vivo and in vitro. In addition, we found that ethanol induced autophagy and cardiac injury largely via the sequential triggering of reactive oxygen species (ROS) accumulation, activation of c-Jun NH2-terminal kinase (JNK), phosphorylation of Bcl-2, and dissociation of the Beclin 1/Bcl-2 complex...
March 28, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28350133/low-shear-stress%C3%A2-induced-autophagy-alleviates-cell-apoptosis-in-huvecs
#13
Guo Dong, Shusen Yang, Xuefei Cao, Nannan Yu, Jiangbo Yu, Xiufen Qu
Low shear stress (LSS) is a well‑established risk factor resulting in endothelial apoptosis and atherosclerosis. Autophagy has been reported to be involved in the development of atherosclerosis. However, whether autophagy participates in LSS‑induced atherosclerosis remains unclear. The effect of autophagy and its association with apoptosis, in the development of atherosclerosis, remains controversial. Therefore, in the present study, the level and role of autophagy in human umbilical vein endothelial cells (HUVECs) exposed to LSS was examined...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28347754/cadmium-disrupts-autophagic-flux-by-inhibiting-cytosolic-ca-2-dependent-autophagosome-lysosome-fusion-in-primary-rat-proximal-tubular-cells
#14
Fei Liu, Xin-Yu Wang, Xu-Ping Zhou, Zong-Ping Liu, Xiang-Bin Song, Zhen-Yong Wang, Lin Wang
Previous studies have shown that subcellular Ca(2+) redistribution is involved in Cd-induced autophagy inhibition in primary rat proximal tubular (rPT) cells, but the mechanism remains unclear. In this study, the status of autophagic flux was monitored by the GFP and RFP tandemly tagged LC3 method. Pharmacological inhibition of cytosolic Ca(2+) concentration ([Ca(2+)]c) with 2-APB or BAPTA-AM significantly alleviated Cd-elevated yellow puncta formation and restored Cd-inhibited red puncta formation, while thapsigargin (TG) had the opposite regulatory effect, demonstrating that Cd-induced [Ca(2+)]c elevation inhibited the autophagic flux in rPT cells...
March 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28337557/mir-9-enhances-the-sensitivity-of-a549-cells-to-cisplatin-by-inhibiting-autophagy
#15
Yan Zhang, Xia Meng, Cheng Li, Zhoulin Tan, Xinwei Guo, Zhiting Zhang, Tao Xi
OBJECTIVES: To demonstrate that miR-9 inhibits autophagy by down-regulating Beclin1 and thus enhances the sensitivity of A549 cells to cisplatin. RESULTS: MiR-9 inhibited Beclin1 expression by binding to its 3'UTR. The inhibition decreased the cisplatin-induced autophagy in A549 cells, evidenced by the decreased expression of LC3II and GFP-LC3 puncta and the increased expression of P62. Upregulation of miR-9 level enhanced the sensibility of A549 cells to cisplatin and increased the cisplatin-induced apoptosis...
March 23, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28323206/ligands-of-peroxisome-proliferator-activated-receptor-alpha-promote-glutamate-transporter-1-endocytosis-in-astrocytes
#16
Hui-Ting Huang, Chih-Kai Liao, Wen-Tai Chiu, Shun-Fen Tzeng
Astrocytes, a stellate-shape glial population in the central nervous system (CNS), maintain glutamate homeostasis in adult CNS by undergoing glutamate uptake at the synapse through their glutamate transporter-1 (GLT-1). Peroxisome proliferator-activated receptor-α (PPARα) can be activated by endogenous saturated fatty acids to regulate astrocytic lipid metabolism and functions. However, it is unclear if PPARα can exert the regulatory action on GLT-1 expression in astrocytes. This study showed that treatment with palmitic acid (PA) and the other two PPARα agonists (GW 7647 and WY 14,643) caused no change in the morphology of astrocytes, whereas membranous GLT-1 protein levels in astrocytes were significantly decreased by PA and PPARα agonists...
March 18, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28323008/sub-chronic-variable-stress-induces-sex-specific-effects-on-glutamatergic-synapses-in-the-nucleus-accumbens
#17
Anna Brancato, Dana Bregman, H Francisica Ahn, Madeline L Pfau, Caroline Menard, Carla Cannizzaro, Scott J Russo, Georgia E Hodes
Men and women manifest different symptoms of depression and under current diagnostic criteria, depression is twice as prevalent in woman. However, little is known of the mechanisms contributing to these important sex differences. Sub-chronic variable stress (SCVS), a rodent model of depression, induces depression-like behaviors in female mice only, modeling clinical evidence of higher susceptibility to mood disorders in women. Accumulating evidence indicates that altered neuroplasticity of excitatory synapses in the nucleus accumbens (NAc) is a key pathophysiological feature of susceptibility to social stress in males...
March 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28322744/basal-ryanodine-receptor-activity-suppresses-autophagic-flux
#18
Tim Vervliet, Isabel Pintelon, Kirsten Welkenhuyzen, Martin D Bootman, Hiroko Bannai, Katsuhiko Mikoshiba, Wim Martinet, Nael Nadif Kasri, Jan B Parys, Geert Bultynck
The inositol 1,4,5-trisphosphate receptors (IP3Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology...
March 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28318635/the-application-of-infrared-imaging-and-optical-coherence-tomography-of-the-lacrimal-punctum-in-patients-undergoing-punctoplasty-for-epiphora
#19
Hannah M Timlin, Pearse A Keane, Geoffrey E Rose, Daniel G Ezra
PURPOSE: To determine the application of imaging the stenotic lacrimal punctum with infrared photographs and optical coherence tomography (OCT) and to identify characteristics of the lacrimal punctum in patients who benefit from punctoplasty. DESIGN: Case-control study. PARTICIPANTS: Twenty patients with epiphora who were listed for punctoplasty and 20 healthy controls. METHODS: Prospectively, 20 patients listed for punctoplasty were asked to rate their epiphora, using the Munk score, before and after punctoplasty...
March 16, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28301277/evidence-that-orai1-does-not-contribute-to-store-operated-trpc1-channels-in-vascular-smooth-muscle-cells
#20
Jian Shi, Francesc Miralles, Jean-Pierre Kinet, Lutz Birnbaumer, William A Large, Anthony P Albert
Ca(2+)-permeable store-operated channels (SOCs) mediate Ca(2+) entry pathways which are involved in many cellular functions such as contraction, growth, and proliferation. Prototypical SOCs are formed of Orai1 proteins and are activated by the endo/sarcoplasmic reticulum Ca(2+) sensor stromal interaction molecule 1 (STIM1). There is considerable debate about whether canonical transient receptor potential 1 (TRPC1) proteins also form store-operated channels (SOCs), and if they do, is Orai1 involved. We recently showed that stimulation of TRPC1-based SOCs involves store depletion inducing STIM1-evoked Gαq/PLCβ1 activity in contractile vascular smooth muscle cells (VSMCs)...
March 16, 2017: Channels
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