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Autophagy and HIF-1

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https://www.readbyqxmd.com/read/28729825/dexmedetomidine-protects-mouse-brain-from-ischemia-reperfusion-injury-via-inhibiting-neuronal-autophagy-through-up-regulating-hif-1%C3%AE
#1
Cong Luo, Ming-Wen Ouyang, Ying-Ying Fang, Shu-Ji Li, Quan Zhou, Jun Fan, Zai-Sheng Qin, Tao Tao
Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28706950/effects-of-cobalt-chloride-a-hypoxia-mimetic-agent-on-autophagy-and-atrophy-in-skeletal-c2c12-myotubes
#2
Rui Chen, Ting Jiang, Yanling She, Jiehua Xu, Cheng Li, Shanyao Zhou, Huijuan Shen, Huacai Shi, Shuang Liu
BACKGROUND: Hypoxia-induced autophagy and muscle wasting occur in several environmental and pathological conditions. However, the molecular mechanisms underlying the effects of the hypoxia-mimetic agent CoCl2 on autophagy and muscle atrophy are still unclear. METHODS: C2C12 myotubes were exposed to increasing concentrations of CoCl2 for 24 hours. Quantitative RT-PCR, Western blotting, and transmission electron microscopy were performed to confirm autophagy occurs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28689810/lincrna-p21-knockdown-enhances-radiosensitivity-of-hypoxic-tumor-cells-by-reducing-autophagy-through-hif-1-akt-mtor-p70s6k-pathway
#3
Yueming Shen, Yingying Liu, Ting Sun, Wei Yang
Hypoxic conditions are common in solid tumors and have a significant effect on tumor progression, therapeutic and prognosis. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides and cannot be translated into proteins, which play important roles in some diseases including cancer. Although previous analysis have showed that long intergenic non-coding RNA (lincRNA)-p21 is hypoxia-responsive and functions as a new regulator of cell cycle, apoptosis and warburg effect in cervical cancer, its biological roles in hypoxic hepatoma and glioma are unknown...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28653874/invalidation-of-mitophagy-by-fbp1-mediated-repression-promotes-apoptosis-in-breast-cancer
#4
Yifeng Liu, Yulin Jiang, Nian Wang, Qianni Jin, Feihu Ji, Changli Zhong, Zhiqiang Zhang, Junhong Yang, Xiangsen Ye, Tingmei Chen
Fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor. However, the functions of fructose-1,6-bisphosphatase 1 in the regulation of mitophagy and apoptosis remain unknown. Here, we investigated the effects of fructose-1,6-bisphosphatase 1 on mitophagy and apoptosis as well as their underlying mechanisms in breast cancer cells. In this work, the messenger RNA and protein expression of various molecules were determined by quantitative realtime polymerase chain reaction and western blot, respectively...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28618416/shock-wave-therapy-promotes-cardiomyocyte-autophagy-and-survival-during-hypoxia
#5
Ling Du, Tao Shen, Bing Liu, Yunhe Zhang, Cong Zhao, Na Jia, Que Wang, Qing He
BACKGROUND: Autophagy plays an important role in cardiovascular disease. Controversy still exists regarding the effect of autophagy on ischemic/hypoxic myocardium. Cardiac shock wave therapy (CSWT) is an effective alternative treatment for refractory ischemic heart disease. Whether CSWT can regulate cardiomyocyte autophagy under hypoxic conditions is not clear. We established a myocardial hypoxia model using the H9c2 cell line and performed shock waves (SWs) treatment to evaluate the effect of SW on autophagy...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#6
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28586054/propofol-reduces-hypoxia%C3%A2-induced-autophagic-cell-death-through-downregulating-hif-1%C3%AE-in-alveolar-epithelial-type-ii-cells-of-rats
#7
Hui-Jie Ning, Hong-Bin Yuan, Hai-Tao Xu, Xing-Ying He
Propofol (2,6‑diisopropylphenol) exerts protective effects on alveolar epithelial type II (ATII) cells, partly through attenuating hypoxia‑induced apoptosis. Autophagy is involved in the activation of apoptosis. Therefore, the present study investigated the modulating effect of propofol against autophagy in ATII cells under hypoxia. Western blot analysis was performed to detect the protein expression of the autophagy molecular marker, microtubule‑associated protein 1 light chain 3 (LC3)‑II, under various conditions...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28559999/hypoxia-inducible-factor-1-%C3%AE-protects-mesenchymal-stem-cells-against-oxygen-glucose-deprivation-induced-injury-via-autophagy-induction-and-pi3k-akt-mtor-signaling-pathway
#8
Bingke Lv, Tian Hua, Feng Li, Jianbang Han, Jie Fang, Limin Xu, Chengmei Sun, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Mesenchymal stem cell (MSC) transplantation is a promising therapeutic strategy for myocardial infarction. The survival rate of the grafted MSCs is limited by the conditions of hypoxia and low nutrient levels. In this study, we investigated the role of hypoxia-inducible factor 1 alpha (Hif-1α) in oxygen-glucose deprivation (OGD)-induced injury in MSCs. Hif-1α was overexpressed or suppressed in MSCs by transfection with a Hif-1α expressing vector or Hif-1α-specific siRNA, respectively. Then MSCs were exposed to OGD, and the changes in cell viability, cell cycle distribution and apoptosis were respectively monitored by MTT assay and flow cytometry...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28439929/the-roles-of-autophagy-and-hypoxia-in-human-inflammatory-periapical-lesions
#9
H Y Huang, W C Wang, P Y Lin, C P Huang, C Y Chen, Y K Chen
AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues, were examined...
April 25, 2017: International Endodontic Journal
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
#10
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...
April 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
#11
COMPARATIVE STUDY
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
#12
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
#13
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
#14
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...
June 2017: 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
#15
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...
February 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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