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Hypoxia-inducible factor

Manhui Zhu, Xiaojuan Liu, Ying Wang, Lili Chen, Li Wang, Xiao Qin, Jiaowen Xu, Lele Li, Yuanyuan Tu, Taohu Zhou, E Song, Aimin Sang
Endothelial dysfunction is a main feature of retinal neovascular diseases which are the leading cause of blindness in developed countries. Yes-associated protein (YAP) and signal transducer and activator of transcription factor 3 (STAT3) participate in angiogenesis via vascular endothelial growth factor (VEGF) signaling. Additionally, YAP can bind STAT3 in endothelial cells. In the study, dimethyloxalylglycine (DMOG) stimulated human retinal microvascular endothelial cells (HRMECs) was used as retinal endothelial hypoxia model...
October 17, 2018: Experimental Cell Research
Nasser Hashemi Goradel, Masoud Najafi, Eniseh Salehi, Bagher Farhood, Keywan Mortezaee
Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo- and radiotherapy. COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells...
October 20, 2018: Journal of Cellular Physiology
Yuanyuan Yan, Fangxiao Liu, Li Han, Lin Zhao, Jianjun Chen, Olufunmilayo I Olopade, Miao He, Minjie Wei
BACKGROUND: Hypoxic tumor microenvironment and maintenance of stemness contribute to drug resistance in breast cancer. However, whether Hypoxia-inducible factor-2α (HIF-2α) in hypoxic tumor microenvironment mediates conversion to a stem cell phenotype and chemoresistance of breast tumors has not been elucidated. METHODS: The mRNA and protein expressions of HIF-1α, HIF-2α, Wnt and Notch pathway were determined using qRT-PCR and western blot. Cell viability and renew ability were assessed by MTT, Flow cytometric analysis and soft agar colony formation...
October 19, 2018: Journal of Experimental & Clinical Cancer Research: CR
Kumar Subramani, Srikrishnan P Raju, Xiaogang Chu, Marie Warren, Chirayu D Pandya, Nasrul Hoda, Sadanand Fulzele, Raghavan Raju
Sepsis affects microcirculation and tissue perfusion leading to tissue hypoxia and multiple organ dysfunction. Red blood cells (RBCs; erythrocytes) are typically biconcave in shape, transport hemoglobin-bound oxygen and are reversibly deformable facilitating trafficking through capillaries. Decreased deformability of RBCs adversely affects tissue oxygenation. The purpose of this project was to determine RBC deformability in a murine model of polymicrobial sepsis by a method that utilizes laser diffraction and microfluidics, and to identify the causative factors in the plasma that may contribute to loss in RBC deformability...
October 16, 2018: International Immunopharmacology
Qiying Fan, Hua Mao, Liang Xie, Xinchun Pi
Acute lung injury and its more severe form, the acute respiratory distress syndrome, are life-threatening respiratory disorders. Overwhelming pulmonary inflammation and endothelium disruption are commonly observed. Endothelial cells (ECs) are well recognized as key regulators in leukocyte adhesion and migration in response to bacterial infection. Prolyl hydroxylase domain (PHD)-2 protein, a major PHD in ECs, plays a critical role in intracellular oxygen homeostasis, angiogenesis, and pulmonary hypertension...
October 16, 2018: American Journal of Pathology
Ji-Young Seok, Yun-Jeong Jeong, Soon-Kyung Hwang, Cheorl-Ho Kim, Junji Magae, Young-Chae Chang
4-O-methylascochlorin (MAC) is a derivative of ascochlorin, a prenyl-phenol compound antibiotic isolated from the fungus Ascochyta viciae. MAC induces caspase/poly (ADP-ribose) polymerase-mediated apoptosis in leukemia cells. However, the effects of MAC on autophagy in cancer cells and the underlying molecular mechanisms remain unknown. Here, we show that MAC induces autophagy in lung cancer cells. MAC significantly induced the expression of autophagy marker proteins including LC3-II, Beclin1, and ATG7. MAC promoted AMP-activated protein kinase (AMPK) phosphorylation and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream signalling proteins P70S6K and 4EBP1...
October 19, 2018: Journal of Cellular and Molecular Medicine
Wentao Yu, Wei Gao, Dan Rong, Zhixian Wu, Raouf A Khalil
Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia and reduced uterine perfusion pressure (RUPP). RUPP causes imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies...
October 19, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Simona Saksonová, Mária Brodňanová, Katarína Dibdiaková, Ivana Pilchová, Katarína Klačanová, Jozef Hatok, Peter Račay
The aim our study was to investigate protective effect of cobalt chloride (CoCl2) in the model of proteasome stress of neuroblastoma SH-SY5Y cells induced by bortezomib, an inhibitor of 26S proteasome. We have focused our interests on Hsp70 and activation of caspase 3. Finally, we have compared the effect of CoCl2 with an effect of the pre-treatment of the cells with 17-AAG, an inhibitor of Hsp90 that is capable to induce expression of Hsp70, or with IOX2, an inhibitor of isoform 2 of prolyl hydroxylase that increases stability of hypoxia inducible factor 1α (HIF1α)...
October 19, 2018: General Physiology and Biophysics
Si-Qian Gao, Chen Chang, Jun-Jun Li, Ying Li, Xiao-Qian Niu, Dan-Ping Zhang, Long-Jian Li, Jian-Qing Gao
Nonhealing chronic wounds on foot induced by diabetes is a complicated pathologic process. They are mainly caused by impaired neovascularization, neuropathy, and excessive inflammation. A strategy, which can accelerate the vessel network formation as well as inhibit inflammatory response at the same time, makes it possible for effective diabetic ulcers treatment. Co-delivery of multiple drugs with complementary bioactivity offers a strategy to properly treat diabetic wound. We previously demonstrated that hydroxysafflor yellow A (HSYA) could accelerate diabetic wound healing through promoting angiogenesis and reducing inflammatory response...
November 2018: Drug Delivery
Thomas Briston, Jenna M Stephen, Luke W Thomas, Cinzia Esposito, Yuen-Li Chung, Saiful E Syafruddin, Mark Turmaine, Lucas A Maddalena, Basma Greef, Gyorgy Szabadkai, Patrick H Maxwell, Sakari Vanharanta, Margaret Ashcroft
Dysregulated mitochondrial function is associated with the pathology of a wide range of diseases including renal disease and cancer. Thus, investigating regulators of mitochondrial function is of particular interest. Previous work has shown that the von Hippel-Lindau tumor suppressor protein (pVHL) regulates mitochondrial biogenesis and respiratory chain function. pVHL is best known as an E3-ubiquitin ligase for the α-subunit of the hypoxia inducible factor (HIF) family of dimeric transcription factors. In normoxia, pVHL recognizes and binds hydroxylated HIF-α (HIF-1α and HIF-2α), targeting it for ubiquitination and proteasomal degradation...
2018: Frontiers in Oncology
Jiang Du, Yong Zhu, Xiaoxiao Meng, Hui Xie, Jinfeng Wang, Zhigang Zhou, Ruilan Wang
AIM: This study investigated the effects of atorvastatin (ATS) on the paraquat (PQ)-induced epithelial-mesenchymal transition (EMT) and the potential mechanism through hypoxia-inducible factor-1 alpha (HIF-1α). MAIN METHODS: Sprague-Dawley (SD) rats were randomly divided into a control group (n = 5), PQ group (n = 20), PQ + ATS L group (n = 20, ATS 20 mg/kg daily) and PQ + ATS H group (n = 20, ATS 40 mg/kg daily). All treated rats were given a 20% PQ solution (50 mg/kg) once by gavage and then sacrificed 12, 24, 72 and 168 h after PQ exposure...
October 15, 2018: Life Sciences
Qing Tang, Ming-Yue Li, Yu-Fei Su, Jia Fu, Zong-Yi Zou, Yi Wang, Shao-Ning Li
Apoptosis of cardiomyocytes and oxidant stress are considered essential processes in the progression of cardiovascular diseases. A hypoxic stress which causes apoptosis of cardiomyocytes is the main problem in ischemic heart disease. The aim of the present study was to explore the functional role and potential mechanisms of miR-223-3p in hypoxia-induced cardiomyocyte apoptosis and oxidative stress. Here, we observed a increment of miR-223-3p level accompanied by the decrease of Krüppel-like zinc-finger transcription factor 15 (KLF15) expression in response to hypoxia...
October 15, 2018: European Journal of Pharmacology
Chuanlong Guo, Lijun Wang, Bo Jiang, Dayong Shi
The bromophenol curcumin analog 1,5-bis(3-bromo-4, 5-dimethoxyphenyl) penta-1, 4-dien-3-one (BCA-5) was assayed for antiangiogenic activity. Tandem mass tag labeling and liquid chromatography-tandem mass spectrometry were used to quantify the dynamic changes in the human umbilical vein endothelial cell (HUVEC) proteome. Functional annotation showed that BCA-5 might inhibit compounds related to the extracellular matrix, compounds that possess cytoskeletal protein-binding activity, and compounds that interact with cell motility-related enzymes, indicating antiangiogenic potential...
November 2018: Anti-cancer Drugs
Md Saydur Rahman, Peter Thomas
Aryl hydrocarbon receptor nuclear translocator (ARNT) is an important transcriptions factor that binds/coactivates drug-metabolizing genes in vertebrates. In this study, we report the cloning and characterization of two ARNT (ARNT-1 and ARNT-2) genes and their mRNA and protein expression in liver tissues of Atlantic croaker after co-exposure to hypoxia and 3,3',4,4'-tetrachlorobiphenyl (PCB77). The full-length croaker ARNT-1 and ARNT-2 genes encode proteins of 537 and 530 amino acids, respectively, and are highly homologous to ARNT-1 and ARNT-2 genes of other vertebrates...
October 18, 2018: Environmental Toxicology
Fahaid Al-Hashem, Suliman Al-Humayed, Shaimaa N Amin, Samaa S Kamar, Soheir S Mansy, Sarah Hassan, Lubna O Abdel-Salam, Mohamed Abd Ellatif, Mohammed Alfaifi, Mohamed A Haidara, Bahjat Al-Ani
The potential inhibitory effect of the antidiabetic and anti-inflammatory drug, metformin on thioacetamide (TAA)-induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)-hypoxia-inducible factor-1α (HIF-1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group)...
October 18, 2018: Journal of Cellular Physiology
Xin Fang, Ru Sun, Yuxin Hu, Huihui Wang, Yi Guo, Bei Yang, Jingbo Pi, Yuanyuan Xu
Chronic exposure to high levels of arsenic has been associated with high risks for many cancers, including renal cell carcinoma (RCC). However the underlying mechanisms are not clear. In the present study, chronic arsenite exposure (2 μM or 5 μM, 30 weeks) induced malignant transformation of HK-2 human renal epithelial cells as indicated by elevated colony formation (6.2- and 5.4-fold increase, respectively), secreted MMP-9 activity (10.1- and 11.3-fold increase, respectively) and proliferation rate (1.2- and 1...
October 18, 2018: Metallomics: Integrated Biometal Science
X Zhao, F Q Yu, X J Huang, B Y Xu, Y L Li, X Y Zhao, H F Guo, B Luan
Asthma is a respiratory disease that affects people of all walks of life, and is a hotspot of continuous research, with significant manpower and resources invested in its study. Airway remodeling is an important associated pathological change, and a mark of the irreversible damage produced by asthma. It involves compositional and functional changes in the cells of the airway walls, leading to reversible structural changes, and complicating treatment. Airway remodeling is mediated by different inflammatory pathways which have been targeted for treatment, with good results...
September 2018: Journal of Biological Regulators and Homeostatic Agents
Xiao-Fei Ding, Jie Chen, Jun Zhou, Guang Chen, Ying-Liang Wu
Previous research has revealed that the von-Hippel-Lindau tumor suppressor protein (pVHL) may downregulate never-in-mitosis A-related kinase 8 (NEK8) via hypoxia-inducible factor-α (HIF-α). The HIF-independent functions of pVHL also serve an important role in its tumor-suppressor action. In the present study, the association between pVHL and NEK8 was demonstrated in the human gastric cancer cell line, SGC-7901, indicating a direct interaction of pVHL with NEK8. Subsequently, it was reported that MG-132, a specific proteasome inhibitor, may attenuate pVHL overexpression-induced reductions in NEK8 protein expression levels...
November 2018: Oncology Letters
Yuqing Zhang, Amanda Kirane, Huocong Huang, Noah B Sorrelle, Francis J Burrows, Michael T Dellinger, Rolf A Brekken
Resistance to standard therapy remains a major challenge in the treatment of pancreatic ductal adenocarcinoma (PDA). Although anti-VEGF therapy delays PDA progression, therapy-induced hypoxia results in a less differentiated mesenchymal-like tumor cell phenotype, which reinforces the need for effective companion therapies. COX-2 inhibition has been shown to promote tumor cell differentiation and improve standard therapy response in PDA. Here, we evaluate the efficacy of COX-2 inhibition and VEGF blockade in preclinical models of PDA...
October 17, 2018: Molecular Cancer Research: MCR
Yihua Wang, Shan Zhong, Christopher J Schofield, Peter J Ratcliffe, Xin Lu
Hypoxia plays a critical role at cellular and physiological levels in all animals. The responses to chronic hypoxia are, at least substantially, orchestrated by activation of the hypoxia inducible transcription factors (HIFs), whose stability and subsequent transcriptional activation are regulated the by HIF hydroxylases. Factor inhibiting HIF (FIH), initially isolated as a HIFα interacting protein following a yeast two-hybrid screen, is an asparaginyl hydroxylase that negatively regulates transcriptional activation by HIF...
October 17, 2018: Journal of Cell Science
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