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Autophagy and HIF-1

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https://www.readbyqxmd.com/read/27856259/potential-suppression-of-the-high-glucose-and-insulin-induced-retinal-neovascularization-by-sirtuin-3-in-the-human-retinal-endothelial-cells
#1
Xin-Bang Mao, Zhi-Peng You, Chen Wu, Jun Huang
Retinal neovascularization generally play roles in the formation of various severe eye diseases, such as age-related macular degeneration and diabetic retinopathy. The regulation of neovascularization-related pathways by Sirtuin 3 (Sirt3), a major mitochondrial NAD(+)-dependent deacetylase, give us a cue that Sirt3 may participate in the retinal neovascularization. However, the mechanism remains unclear. Here, we established a retinal neovascularization model by using human retinal endothelial cells (HRECs) under the induction of high glucose and insulin (HGI)...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27800505/fifteen-days-of-3-200-m-simulated-hypoxia-marginally-regulates-markers-for-protein-synthesis-and-degradation-in-human-skeletal-muscle
#2
Gommaar D'Hulst, Alessandra Ferri, Damien Naslain, Luc Bertrand, Sandrine Horman, Marc Francaux, David J Bishop, Louise Deldicque
Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible factor (HIF) pathway. Eight young male subjects lived in a normobaric hypoxic hotel (FiO2 14.1%, 3,200 m) for 15 days in well-controlled conditions for nutrition and physical activity...
2016: Hypoxia
https://www.readbyqxmd.com/read/27698862/aspirin-may-inhibit-angiogenesis-and-induce-autophagy-by-inhibiting-mtor-signaling-pathway-in-murine-hepatocarcinoma-and-sarcoma-models
#3
Qianqian Zhao, Zhaopeng Wang, Zhaoxia Wang, Licun Wu, Weidong Zhang
Aspirin is known to have inhibitory effects on growth development in various types of tumor. In previous studies, it was observed to inhibit angiogenesis by downregulating the expression of vascular endothelial growth factor-A (VEGF-A). In the present study, murine H22 hepatocarcinoma and S180 sarcoma models were used to ascertain whether aspirin could inhibit angiogenesis and promote autophagy in tumors. Tumor-bearing mice were randomly divided into four groups with 10 mice per group: i) no treatment; ii) low-dose aspirin (100 mg/kg); iii) high-dose aspirin (400 mg/kg); iv) everolimus group (4 mg/kg)...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27687210/lack-of-mitochondrial-dna-impairs-chemical-hypoxia-induced-autophagy-in-liver-tumor-cells-through-ros-ampk-ulk1-signaling-dysregulation-independently-of-hif-1%C3%AE
#4
Jose J G Marin, Elisa Lozano, Maria J Perez
Alterations in mitochondrial DNA (mtDNA) and autophagy activation are common events in tumors. Here we have investigated the effect of mitochondrial genome depletion on chemical hypoxia-induced autophagy in liver tumor cells. Human SK-Hep-1 wild-type and mtDNA-depleted (Rho) cells were exposed to the hypoxia mimetic agents CoCl2 and deferoxamine (DFO). Up-regulation of HIF-1α, but not HIF-2α was observed. The expression of several HIF-1α target genes was also found. In human SK-Hep-1 and mouse Hepa 1-6 liver tumor cells, but not in the counterpart Rho derived lines, chemical hypoxia increased the abundance of autophagosomes and autolysosomes...
September 26, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27678081/the-role-of-hypoxia-inducible-factor-1%C3%AE-in-zinc-oxide-nanoparticle-induced-nephrotoxicity-in-vitro-and-in-vivo
#5
Yuh-Feng Lin, I-Jen Chiu, Fong-Yu Cheng, Yu-Hsuan Lee, Ying-Jan Wang, Yung-Ho Hsu, Hui-Wen Chiu
BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. RESULTS: We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation...
September 27, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27527871/prolyl-hydroxylase-2-phd2-inhibition-protects-human-renal-epithelial-cells-and-mice-kidney-from-hypoxia-injury
#6
Yi Fang, Hui Zhang, Yihong Zhong, Xiaoqiang Ding
Prolyl hydroxylase domain protein 2 (PHD2) is a key oxygen sensor, setting low steady-state level of hypoxia-inducible factor-α (HIF-α). Here, we showed that treatment of cobalt chloride (CoCl2), a hypoxia mimic, in HK-2 tubular epithelial cells induced PHD2 and HIF-1/2α expression as well as cell apoptosis and autophagy activation. Three methyladenine (3-MA), the autophagy inhibitor, blocked autophagy and protected HK-2 cells from CoCl2. Significantly, siRNA knockdown of PHD2 also protected HK-2 cells from CoCl2,possibly via increasing HIF-1α expression...
August 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27430964/luteolin-decreases-the-uva%C3%A2-induced-autophagy-of-human-skin-fibroblasts-by-scavenging-ros
#7
Miaomiao Yan, Zhongrong Liu, Huilan Yang, Cuihua Li, Hulin Chen, Yan Liu, Minling Zhao, Yingjie Zhu
Luteolin (LUT) is a flavone, which is universally present as a constituent of traditional Chinese herbs, and certain vegetables and spices, and has been demonstrated to exhibit potent radical scavenging and cytoprotective properties. Although LUT has various beneficial effects on health, the effects of LUT on the protection of skin remain to be fully elucidated. The present study investigated whether LUT can protect human skin fibroblasts (HSFs) from ultraviolet (UV) A irradiation. It was found that, following exposure to different doses of UVA irradiation, the HSFs exhibited autophagy, as observed by fluorescence and transmission electron microscopy, and reactive oxygen species (ROS) bursts, analyzed by flow cytometry, to differing degrees...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27417236/g9a-inhibition-induced-pkm2-regulates-autophagic-responses
#8
Fahim Ahmad, Deobrat Dixit, Shanker Datt Joshi, Ellora Sen
Epigenetic regulation by histone methyltransferase G9a is known to control autophagic responses. As the link between autophagy and metabolic homeostasis is widely accepted, we investigated whether G9a affects metabolic circuitries to affect autophagic response in glioma cells. Both pharmacological inhibition and siRNA mediated knockdown of G9a increased autophagy marker LC3B in glioma cells. G9a inhibitor BIX-01294 (BIX) induced Akt-dependent increase in HIF-1α expression and activity. Inhibition of Akt-HIF-1α axis reversed BIX-mediated (i) increase in LC3B expression and (ii) decrease in Yes-associated protein 1 (YAP1) phosphorylation...
September 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27405163/-sodium-nitrite-enhanced-the-potentials-of-migration-and-invasion-of-human-hepatocellular-carcinoma-smmc-7721-cells-through-induction-of-mitophagy
#9
Guan Gui, Shan-shan Meng, Lu-juan Li, Bin Liu, Hong-xia Liang, Chao-shen Huangfu
Nitrites play multiple characteristic functions in invasion and metastasis of hepatic cancer cells, but the exact mechanism is not yet known. Cancer cells can maintain the malignant characteristics via clearance of excess mitochondria by mitophagy. The purpose of this article was to determine the roles of nitrite, reactive oxygen species (ROS) and hypoxia inducing factor 1 alpha (HIF-1 α) in mitophagy of hepatic cancer cells. After exposure of human hepatocellular carcinoma SMMC-7721 cells to a serial concentrations of sodium nitrite for 24 h under normal oxygen, the maximal cell vitality was increased by 16 mg x (-1) sodium nitrite...
January 2016: Yao Xue Xue Bao, Acta Pharmaceutica Sinica
https://www.readbyqxmd.com/read/27366871/hypoxia-suppresses-myocardial-survival-pathway-through-hif-1%C3%AE-igfbp-3-dependent-signaling-and-enhances-cardiomyocyte-autophagic-and-apoptotic-effects-mainly-via-foxo3a-induced-bnip3-expression
#10
Chih-Chung Feng, Chien-Chung Lin, Yi-Ping Lai, Tung-Sheng Chen, Shibu Marthandam Asokan, Jing-Ying Lin, Kuan-Ho Lin, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
The HIF-1α transcriptional factor and the BH-3 only protein BNIP3 are known to play fundamental roles in response to hypoxia. The objective of this research is to investigate the molecular mechanisms and the correlation of HIF-1α, BNIP3 and IGFBP-3 in hypoxia-induced cardiomyocytes injuries. Heart-derived H9c2 cells and neonatal rat ventricular myocytes (NRVMs) were incubated in normoxic or hypoxic conditions. Hypoxia increased HIF-1α expression and activated the downstream BNIP3 and IGFBP-3 thereby triggered mitochondria-dependent apoptosis...
August 2016: Growth Factors
https://www.readbyqxmd.com/read/27284306/hypoxia-induces-autophagy-in-cardiomyocytes-via-a-hypoxia-inducible-factor-1-dependent-mechanism
#11
Lan Gui, Batu Liu, Guang Lv
Hypoxia frequently accompanies such vascular disorders as atherosclerosis, thrombosis and ischemia/reperfusion injury. Myocardial ischemia/reperfusion, in particular, is a major contributor to cardiomyocyte impairment. Autophagy is a dynamic, self-catabolic process that has been implicated in a wide range of physiological processes and the pathogenesis of diverse diseases. The aim of the present study was to investigate the promotion of autophagy by hypoxia in a rat H9c2 heart cell line and determine the regulatory role of hypoxia-inducible factor 1 (HIF-1) in the hypoxia-induced autophagy in H9c2 cells, using quantitative green fluorescent protein-microtubule-associated protein 1 light chain 3 analysis and electron microscopy of autophagic vesicles...
June 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27220494/mir-21-modulates-radiosensitivity-of-cervical-cancer-through-inhibiting-autophagy-via-the-pten-akt-hif-1%C3%AE-feedback-loop-and-the-akt-mtor-signaling-pathway
#12
Lili Song, Shikai Liu, Liang Zhang, Hairong Yao, Fangyuan Gao, Dongkui Xu, Qian Li
MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression...
May 25, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27114850/hypoxia-inducible-histone-lysine-demethylases-impact-on-the-aging-process-and-age-related-diseases
#13
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia...
March 2016: Aging and Disease
https://www.readbyqxmd.com/read/27109098/hypoxia-induced-oxidative-stress-promotes-muc4-degradation-via-autophagy-to-enhance-pancreatic-cancer-cells-survival
#14
S Joshi, S Kumar, M P Ponnusamy, S K Batra
Pancreatic cancer (PC) and associated pre-neoplastic lesions have been reported to be hypoxic, primarily due to hypovascular nature of PC. Though the presence of hypoxia under cancerous condition has been associated with the overexpression of oncogenic proteins (MUC1), multiple emerging reports have also indicated the growth inhibitory effects of hypoxia. In spite of being recognized as the top-most differentially expressed and established oncogenic protein in PC, MUC4 regulation in terms of micro-environmental stress has not been determined...
November 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27082295/prolyl-4-hydroxylases-inhibitor-stabilizes-hif-1%C3%AE-and-increases-mitophagy-to-reduce-cell-death-after-experimental-retinal-detachment
#15
Haiyang Liu, Hong Zhu, Tong Li, Pengfei Zhang, Ning Wang, Xiaodong Sun
PURPOSE: This study investigated the neuroprotective effect against photoreceptor cell death using prolyl-4-hydroxylases inhibitor (PHI), an HIF-1α stabilizer, in experimental retinal detachment (RD). METHODS: RD was created in Brown Norway rats by subretinal injection of 1% sodium hyaluronate. FG-4592 (a PHI, 25 mg/kg) or a vehicle was administered every 2 days with retro-orbital injection. Photoreceptor death was evaluated by TdT-dUTP terminal nick-end labeling (TUNEL) assay 3 days after RD and by the thickness of the outer nuclear layer 7 days after RD...
April 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27074563/hinokitiol-protects-primary-neuron-cells-against-prion-peptide-induced-toxicity-via-autophagy-flux-regulated-by-hypoxia-inducing-factor-1
#16
Ji-Hong Moon, Ju-Hee Lee, You-Jin Lee, Sang-Youel Park
Prion diseases are fatal neurodegenerative disorders that are derived from structural changes of the native PrPc. Recent studies indicated that hinokitiol induced autophagy known to major function that keeps cells alive under stressful conditions. We investigated whether hinokitiol induces autophagy and attenuates PrP (106-126)-induced neurotoxicity. We observed increase of LC3-II protein level, GFP-LC3 puncta by hinokitiol in neuronal cells. Addition to, electron microscopy showed that hinokitiol enhanced autophagic vacuoles in neuronal cells...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27040799/prolidase-proline-dehydrogenase-proline-oxidase-collagen-biosynthesis-axis-as-a-potential-interface-of-apoptosis-autophagy
#17
REVIEW
Ilona Zareba, Jerzy Palka
Prolidase is a cytosolic imidodipeptidase that specifically splits imidodipeptides with C-terminal proline or hydroxyproline. The enzyme plays an important role in the recycling of proline from imidodipeptides for resynthesis of collagen and other proline-containing proteins. The mechanism of prolidase-dependent regulation of collagen biosynthesis was found at both transcriptional and post-transcriptional level. The increase in the enzyme activity is due to its phosphorylation on serine/threonine residues. Prolidase-dependent transcriptional regulation of collagen biosynthesis was found at the level of NF-κB, known inhibitor of type I collagen gene expression...
July 8, 2016: BioFactors
https://www.readbyqxmd.com/read/27035851/inhibitory-role-of-trip-br1-oncoprotein-in-hypoxia-induced-apoptosis-in-breast-cancer-cell-lines
#18
Chengping Li, Samil Jung, Young Yang, Keun-Il Kim, Jong-Seok Lim, Chung-Il Cheon, Myeong-Sok Lee
TRIP-Br1 oncoprotein is known to be involved in many vital cellular functions. In this study, we examined the role of TRIP-Br1 in hypoxia-induced cell death. Exposure to the overcrowded and CoCl2-induced hypoxic conditions increased TRIP-Br1 expression at the protein level in six breast cancer cell lines (MCF7, MDA-MB-231, T47D, Hs578D, BT549, and MDA-MB-435) but resulted in no significant change in three normal cell lines (MCF10A, MEF and NIH3T3). Our result revealed that CoCl2-induced hypoxia stimulated apoptosis and autophagy, in which TRIP-Br1 expression was found to be upregulated...
June 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27031712/hif-1-a-big-chapter-in-the-cancer-tale
#19
J Ajduković
Approximately 1.0-1.5% of the genome is transcriptionally regulated by hypoxia, and hypoxia-inducible factor (HIF)-1α is the transcription factor modulating many of these genes. Cancer cells are able to survive hypoxic environments and hypoxia itself can activate adaptive cellular responses that contribute to tumor progression. Many HIF-1α-mediated biological effects are beneficial for tumor progression, including metabolic shift toward glycolysis, inhibition of fatty acid β-oxidation, production of cellular reactive oxygen species and altering expression of tumor suppressor genes...
March 2016: Experimental Oncology
https://www.readbyqxmd.com/read/26914112/hypoxia-responsive-mir-210-promotes-cell-survival-and-autophagy-of-endometriotic-cells-in-hypoxia
#20
T-X Xu, S-Z Zhao, M Dong, X-R Yu
OBJECTIVE: Hypoxia may play a role in the survival of ectopic endometrial cells. This study aimed to explore how hypoxia responsive miR-210 is involved in cell survival and autophagic response of endometriotic cells. MATERIALS AND METHODS: The expression of hypoxia-inducible factor 1-alpha (HIF-1α) and miR-210 in eutopic and ectopic endometrial tissues were measured. The expression changes of HIF-1α and miR-210 in ovarian endometriotic cell line CRL-7566 after hypoxic culture were further explored...
2016: European Review for Medical and Pharmacological Sciences
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