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Autophagy and HIF-1

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https://www.readbyqxmd.com/read/28259912/role-of-hypoxia%C3%A2-inducible-factor%C3%A2-1%C3%AE-in-autophagic-cell-death-in-microglial-cells-induced-by-hypoxia
#1
Xintao Wang, Jun Ma, Qiang Fu, Lei Zhu, Zhiling Zhang, Fan Zhang, Nan Lu, Aimin Chen
Microglial cells are phagocytic cells of the central nervous system (CNS) and have been proposed to be a primary component of the innate immune response and maintain efficient CNS homeostasis. Microglial cells are activated during various phases of tissue repair and participate in various pathological conditions in the CNS. Following spinal cord injury (SCI), anoxemia is a key problem that results in tissue destruction. Hypoxia‑inducible factor 1‑α (HIF‑1α) may protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28202394/platelet-rich-plasma-prp-induces-chondroprotection-via-increasing-autophagy-anti-inflammatory-markers-and-decreasing-apoptosis-in-human-osteoarthritic-cartilage
#2
Mayssam Moussa, Daniel Lajeunesse, George Hilal, Oula El Atat, Gaby Haykal, Rim Serhal, Antonio Chalhoub, Charbel Khalil, Nada Alaaeddine
OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration...
March 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28150141/role-of-second-hand-smoke-shs-induced-proteostasis-autophagy-impairment-in-pediatric-lung-diseases
#3
Neel Patel, Christopher D Trumph, Manish Bodas, Neeraj Vij
BACKGROUND: Exposure to second-hand tobacco smoke (SHS) is one of the prime risk factors for chronic lung disease development. Smoking during pregnancy may lead to birth defects in the newborn that include pulmonary dysfunction, increased susceptibility to opportunistic pathogens, or initiation of childhood respiratory manifestations such as bronchopulmonary dysplasia (BPD). Moreover, exposure to SHS in early childhood can have negative impact on lung health, although the exact mechanisms are unclear...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#4
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28017540/transcription-factor-eb-expression-in-early-breast-cancer-relates-to-lysosomal-autophagosomal-markers-and-prognosis
#5
Alexandra Giatromanolaki, Efthimios Sivridis, Dimitra Kalamida, Michael I Koukourakis
BACKGROUND: Disrupting the autophagic balance to trigger autophagic death may open new strategies for cancer therapy. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and may play a role in cancer biology and clinical behavior. METHODS: The expression of TFEB and the lysosomal cancer cell content (expression of lysosomal associated membrane protein 2a [LAMP2a] and cathepsin D) was studied in a series of 100 T1-stage breast carcinomas...
November 23, 2016: Clinical Breast Cancer
https://www.readbyqxmd.com/read/27987381/hypoxia-ischemia-activate-processing-of-amyloid-precursor-protein-impact-of-vascular-dysfunction-in-the-pathogenesis-of-alzheimer-s-disease
#6
REVIEW
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
Alzheimer's disease (AD) is associated with deficiencies in cerebrovascular functions, e.g. reduced cerebral blood flow and capillary amyloid angiopathy, both of which are evident during the early phase of AD, thus local hypoxia/ischemia could augment the pathogenesis of AD. There is abundant literature revealing that exposures to hypoxia/ischemia increase the amyloidogenic processing of amyloid-β precursor protein (APP) leading to the accumulation of amyloid-β peptides in brain. This hypoxia-induced response has been attributed to a significant increase in the activities of β- and γ-secretases, whereas α-secretase activity decreases in hypoxia...
December 17, 2016: Journal of Neurochemistry
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
#7
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)...
January 8, 2017: 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
#8
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
#9
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
#10
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...
December 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
#11
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
#12
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 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27430964/luteolin-decreases-the-uva%C3%A2-induced-autophagy-of-human-skin-fibroblasts-by-scavenging-ros
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
September 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
#19
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
#20
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
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