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Hypoxia-inducible factor

Cun-En Wu, Yu-Wen Zhuang, Jin-Yong Zhou, Shen-Lin Liu, Xi Zou, Jian Wu, Rui-Ping Wang, Peng Shu
The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1...
February 14, 2019: Biological Chemistry
Tao Wang, Li-Ni Zeng, Zhe Zhu, Yu-Hui Wang, Lu Ding, Wei-Bin Luo, Xiao-Min Zhang, Zhi-Wei He, Hong-Fu Wu
Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5-7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion...
June 2019: Neural Regeneration Research
Yuki Onishi, Manami Hiraiwa, Hikari Kamada, Takashi Iezaki, Takanori Yamada, Katsuyuki Kaneda, Eiichi Hinoi
An imbalance of branched-chain amino acids (BCAAs) in the brain may result in neuropathological conditions, such as autism spectrum disorders. The L-type amino acid transporter 1 (LAT1), encoded by the solute carrier transporter 7a5 ( Slc7a5 ) gene, is critical for maintaining normal levels of BCAAs in the brain. However, our understanding of the mechanisms that regulate the expression of LAT1/ Slc7a5 in neurons is currently limited. Here, we demonstrate that hypoxic conditions result in upregulated expression of Slc7a5 in differentiated neuronal cells (Neuro2A cells induced to differentiate using all- trans retinoic acid)...
February 2019: FEBS Open Bio
Jun Wang, Qi Wu, Jianxin Qiu
Clear cell renal cell carcinoma (ccRCC) is characterized by the activation of hypoxia-inducible factors and enhanced aerobic glycolysis. In our previous study, metabolic profiling revealed a threefold increase of fructose 1,6-bisphosphate (FBP) in ccRCC tissue compared with normal kidney tissue. As an important intermediate metabolite, its role in cancer development remains unknown. We found that high levels of FBP were required for cancer growth because of its ability to affect the redox status. Mechanistically, FBP regulated the redox status partially by suppressing NADPH oxidase isoform NOX4 activity in ccRCC cells...
February 13, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
Anna Sonja Müller, Milot Gashi, Klara Janjić, Michael Edelmayer, Andreas Moritz, Hermann Agis
Thixotropic clays have favorable properties for tissue regeneration. Hypoxia mimetic agents showed promising results in pre-clinical models for hard and soft tissue regeneration. It is unclear if clays can be used as carrier for hypoxia mimetic agent in a periodontal regenerative setting. Here, we tested the response of human fibroblasts of the periodontal soft tissue to synthetic clay hydrogels and assessed hypoxia mimetic agent release. Cells were cultured on synthetic clay hydrogels (5.00%-0.15%). We assessed viability and differentiation capacity with resazurin-based toxicity assays, MTT staining, Live-Dead staining, and alkaline phosphatase staining...
February 13, 2019: Journal of Biomaterials Applications
Shahana Perveen, Kamesh Ayyasola, Nahla Zagloul, Hardik Patel, Kanta Ochani, David Orner, Helene Benveniste, Michael Salerno, Paul Vaska, Zhang Zuo, Yousef Alabed, Mansoor Nasim, Edmund J Miller, Mohamed Ahmed
BACKGROUND: Congenital diaphragmatic hernia (CDH) is a complex birth anomaly with significant mortality and morbidity. Lung hypoplasia and persistent pulmonary hypertension (PPHN) limit survival in CDH. Macrophage migration inhibitory factor (MIF), a key regulator of innate immunity, is involved in hypoxia-induced vascular remodeling and PPHN. We hypothesized that antenatal inhibition of MIF in CDH fetuses, would reduce vascular remodeling, and improve angiogenesis and lung development...
February 13, 2019: Pediatric Research
Zhan-Ning Xu, Guo-Dong Zheng, Cheng-Bin Wu, Xia-Yun Jiang, Shu-Ming Zou
Two-dimensional gel electrophoresis (2-DE) was combined with liquid chromatography-mass spectrometry (LC-MS/MS) to identify the differential proteomics of grass carp gills after hypoxic stress to better understand the roles of proteins in the hypoxic response and to explore the possible molecular mechanisms. Protein spots were obtained from a hypoxia-stressed group (372 ± 11 individuals) and a control group (406 ± 14 individuals) using the lmage Master 2D Platinum 7.0 analysis software. Fifteen protein spots were expressed differentially in the hypoxia-stressed group and varied significantly after exposure to the hypoxic conditions...
February 13, 2019: Fish Physiology and Biochemistry
Ying Xiong, Li Liu, Yu Xia, Yangyang Qi, Yifan Chen, Lingli Chen, Peipei Zhang, Yunyi Kong, Yang Qu, Zewei Wang, Zhiyuan Lin, Xiang Chen, Zhuoyi Xiang, Jiajun Wang, Qi Bai, Weijuan Zhang, Yuanfeng Yang, Jianming Guo, Jiejie Xu
PURPOSE: Hypoxia-inducible factor 2α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mechanisms. EXPERIMENTAL DESIGN: We immunohistochemically evaluated immune cells infiltrations and prognostic value of HIF-2α expression in a retrospective Zhongshan Hospital cohort of 280 ccRCC patients...
February 13, 2019: Cancer Immunology, Immunotherapy: CII
Xuechao Yang, Linfei Zhang, Huan Liu, Yongfeng Shao, Shijiang Zhang
Background Chronic intermittent hypoxia ( CIH ) is a distinct pathological mechanism of obstructive sleep apnea ( OSA ), which is recognized as an independent risk factor for cardiovascular diseases. The aims of this study were to ascertain whether CIH induces atrial fibrillation ( AF ), to determine whether cardiac sympathetic denervation ( CSD ) can prevent it and suppress blood pressure, and to explore the potential molecular mechanisms involved. Methods and Results Sixty Sprague-Dawley male rats were randomly divided into 4 groups: sham, CSD , CIH , CIH + CSD ...
February 19, 2019: Journal of the American Heart Association
Li Zhang, Li Zhang, Zhengquan Huang, Runlin Xing, Xiaochen Li, Songjiang Yin, Jun Mao, Nongshan Zhang, Wei Mei, Liang Ding, Peimin Wang
Fibroblast-like synoviocytes (FLSs) are the main effector cells of knee osteoarthritis (KOA) synovial fibrosis. Our last report showed that NLRP1 and NLRP3 inflammasomes may mediate LPS/ATP-induced FLSs pyroptosis in KOA. In the present study, we found an elevated hypoxia-inducible factor-1 α (HIF-1 α ) level in the synovial tissue of KOA model rats, and inhibiting the increase of HIF-1 α could improve synovial fibrosis in rats. Subsequently, we established LPS/ATP-induced model in FLSs mimicking the inflammatory environment of KOA...
2019: Oxidative Medicine and Cellular Longevity
Nak-Kyun Soung, Hye-Min Kim, Yukihiro Asami, Dong Hyun Kim, Yangrae Cho, Ravi Naik, Yerin Jang, Kusic Jang, Ho Jin Han, Srinivas Rao Ganipisetti, Hyunjoo Cha-Molstad, Joonsung Hwang, Kyung Ho Lee, Sung-Kyun Ko, Jae-Hyuk Jang, In-Ja Ryoo, Yong Tae Kwon, Kyung Sang Lee, Hiroyuki Osada, Kyeong Lee, Bo Yeon Kim, Jong Seog Ahn
Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460...
February 12, 2019: Experimental & Molecular Medicine
Felicitas Bossler, Bianca J Kuhn, Thomas Günther, Stephen J Kraemer, Prajakta Khalkar, Svenja Adrian, Claudia Lohrey, Angela Holzer, Mitsugu Shimobayashi, Matthias Dürst, Arnulf Mayer, Frank Rösl, Adam Grundhoff, Jeroen Krijgsveld, Karin Hoppe-Seyler, Felix Hoppe-Seyler
Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia...
February 12, 2019: MBio
Muhannad Abu-Remaileh, Monther Abu-Remaileh, Rania Akkawi, Ibrahim Knani, Shiran Udi, Micheal E Pacold, Joseph Tam, Rami I Aqeilan
OBJECTIVE: WWOX, a well-established tumor suppressor, is frequently lost in cancer and plays important roles in DNA damage response and cellular metabolism. METHODS: We re-analyzed several genome-wide association studies (GWAS) using the Type 2 Diabetes Knowledge Portal website to uncover WWOX's association with metabolic syndrome (MetS). Using several engineered mouse models, we studied the effect of somatic WWOX loss on glucose homeostasis. RESULTS: Several WWOX variants were found to be strongly associated with MetS disorders...
January 31, 2019: Molecular Metabolism
Pinglan Lin, Ming Wu, Junyan Qin, Jing Yang, Chaoyang Ye, Chen Wang
BACKGROUND: Magnesium lithospermate B (MLB) can promote renal microcirculation. The aim of the current project was to study whether MLB improves renal hemodynamics, oxygen consumption and subsequently attenuates hypoxia in rats induced by 5/6th renal Ablation/Infarction(A/I). METHODS: Chronic renal failure (CRF) was induced in male SD rats by the 5/6 (A/I) surgery. 30 rats were randomly divided into three groups: sham group, 5/6 (A/I) + vehicle group (CRF group) and 5/6 (A/I) + MLB (CRF + MLB) group...
February 12, 2019: BMC Nephrology
Iman Azimi, Michael J G Milevskiy, Silke B Chalmers, Kunsala T D S Yapa, Mélanie Robitaille, Christopher Henry, Gregory J Baillie, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith
The remodeling of specific calcium-permeable ion channels is a feature of some breast cancer subtypes. ORAI1 is a protein that forms a calcium-permeable ion channel responsible for store-operated calcium entry (SOCE) in a variety of cell types. ORAI3, a related isoform, is not a regulator of SOCE in most cell types. However, ORAI3 does control SOCE in many estrogen receptor-positive breast cancer cell lines, where it also controls proliferation. ORAI1 is a well-characterized regulator of the proliferation and migration of many basal breast cancer cells; however, the role of ORAI3 in these types of breast cancer cells remains unclear...
February 11, 2019: Cancers
Xiufeng Yu, Xijuan Zhao, Junting Zhang, YiYing Li, Ping Sheng, Cui Ma, Lixin Zhang, XueWei Hao, XiaoDong Zheng, Yan Xing, Hui Qiao, Lihui Qu, Daling Zhu
Accumulating evidence suggests that epidermal growth factor receptor (EGFR) plays a role in the progression of pulmonary arterial hypertension (PAH). Clinically-approved epidermal growth factor inhibitors such as gefitinib, erlotinib, and lapatinib have been explored for PAH . However, None of them were able to attenuate PAH . So, we explored the role of dacomitinib, a new pan-EGFR inhibitor, in PAH. Adult male Sprague-Dawley rats were used to study hypoxia- or monocrotaline-induced right ventricular remodeling as well as systolic function and hemodynamics using echocardiography and a pressure-volume admittance catheter...
February 9, 2019: European Journal of Pharmacology
C B Item, A Schanzer, T Metz, S Greber-Platzer, J Lischka
OBJECTIVES: Elevated levels of metabolites such as ammonia and propionylcarnitine in propionic acidemia (PA) lead to an increased reactive oxygen species (ROS) production which could activate and stabilize the epigenetic regulated hypoxia-inducible factor-1α (HIF-1α). In order to evaluate the DNA methylation status of the HIF-1α binding site in PA, we investigated the antioxidant gluthatione peroxidase 3 gene (GPX3) promoter region. DESIGN AND METHODS: Using leukocyte DNA extracted from bloodspots collected 2-4 days after birth from diet free newborns, the cytosine phosphodiester bond guanine (CpG) dinucleotides of a HIF-1α binding site (CGTTTTTTACG) in the promoter region of GPX3 was retrospectively analysed...
February 9, 2019: Clinical Biochemistry
Katarzyna Magierowska, Dominik Bakalarz, Dagmara Wójcik, Anna Chmura, Magdalena Hubalewska-Mazgaj, Sabina Licholai, Edyta Korbut, Slawomir Kwiecien, Zbigniew Sliwowski, Grzegorz Ginter, Tomasz Brzozowski, Marcin Magierowski
BACKGROUND AND PURPOSE: Besides hydrogen sulfide (H2 S) and nitric oxide (NO), carbon monoxide (CO) contributes to the maintenance of gastric mucosal integrity. We investigated increased CO bioavailability effects on time-dependent dynamics of gastric ulcer healing mediated by particular growth factors, anti-inflammatory and molecular pathways. EXPERIMENTAL APPROACH: Wistar rats with gastric ulcers induced by serosal acetic acid application (day 0) were treated i...
February 9, 2019: Biochemical Pharmacology
Ken Ling, Ancong Xu, Yunfei Chen, Xueyin Chen, Yiqing Li, Weici Wang
Restenosis is liable to occur following treatment with endovascular interventional therapy. Increasing evidence indicates that hydrogen sulfide (H2S) exhibits numerous physiological properties, including antioxidative and cardioprotective disease properties. Thus, the present study aimed to investigate the anti‑restenosis effects of H2S and its protective mechanisms. A balloon dilatation restenosis model was used, in which model Sprague‑Dawley rats were treated with sodium hydrosulfide (NaHS: A donor of H2S, 30 µmol/kg) by intraperitoneal injection for 4 weeks...
January 23, 2019: International Journal of Molecular Medicine
Amita Ajit, Santhoshkumar Thankayyan Retnabai, Lissy K Krishnan
Biotechnological interventions to engineer favorable biochemical environments that facilitate wound repair through quick attainment of vasculature are of immense demand. Potential of angiogenic factors (AF), notably vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (Hif-1α) and the paracrine role of human adipose derived mesenchymal stromal cells (hADMSCs) in establishing vasculature has been reported. Independent application of AF or hADMSCs has led to clinical failure, pertaining to poor means of delivery, deprived bioavailability and insufficiency to drive adequate angiogenesis, respectively...
February 12, 2019: Tissue Engineering. Part C, Methods
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