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Hypoxia induced factor

Suguru Fukushima, Makoto Endo, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Tomoya Matsunobu, Ken-Ichi Kawaguchi, Nokitaka Setsu, Keiichiro IIda, Nobuhiko Yokoyama, Makoto Nakagawa, Kenichiro Yahiro, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima
[This corrects the article DOI: 10.1371/journal.pone.0178064.].
2018: PloS One
Giulia Ravasi, Sara Pelucchi, Gaia Buoli Comani, Federico Greni, Raffaella Mariani, Irene Pelloni, Silvia Bombelli, Roberto Perego, Donatella Barisani, Alberto Piperno
OBJECTIVE: During hypoxia hepcidin expression is inhibited to allow iron mobilization to sustain erythropoietic expansion. We analysed molecular mechanisms underlying hypoxia-induced hepcidin inhibition in an in vivo model of acute hypoxia. METHODS: Mice were kept under normal or hypoxic conditions for 6h and 15h and treated with α-PDGF-BB antibody or PDGF-BB receptor inhibitor. Blood, liver, spleen, and bone marrow were collected to extract RNA and protein or to quantify EPO and PDGF-BB...
March 15, 2018: European Journal of Haematology
Charles K Davis, Sreekala S Nampoothiri, G K Rajanikant
The constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay...
March 14, 2018: Molecular Neurobiology
S Y N Jamaludin, I Azimi, F M Davis, A A Peters, T J Gonda, E W Thompson, S J Roberts-Thomson, G R Monteith
CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells...
April 2018: Oncology Letters
Qiongyuan Hu, Jianan Ren, Guanwei Li, Jie Wu, Xiuwen Wu, Gefei Wang, Guosheng Gu, Huajian Ren, Zhiwu Hong, Jieshou Li
Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls...
March 14, 2018: Cell Death & Disease
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
Rong Jin, Qing-Gang Zhu, Xin-Yue Shen, Miao-Miao Wang, Wajeeha Jamil, Donald Grierson, Xue-Ren Yin, Kun-Song Chen
Artificial high-CO2 atmosphere (AHCA, 95% CO2 and 1% O2) has been widely applied as a postharvest de-astringency treatment for persimmon fruit. AHCA increases expression of transcription factors, including ethylene response factors (DkERF), that target de-astringency genes. Here, the promoter of DkERF9, a previously characterized AHCA-inducible and de-astringency regulator, was utilized to screen a cDNA library by yeast one hybrid assay. A novel NAC transcription factor, named DkNAC7, was identified. Dual-luciferase assay indicated that DkNAC7 could not only trans-activate the promoter of DkERF9, but also activated the previously identified deastringency-related gene DkPDC2...
2018: PloS One
Genta Ochi, Yusuke Kanazawa, Kazuki Hyodo, Kazuya Suwabe, Takeshi Shimizu, Takemune Fukuie, Kyeongho Byun, Hideaki Soya
Although it has been traditionally thought that decreasing SpO2 with ascent to high altitudes not only induces acute mountain sickness but also can decrease executive function, the relationship between decreased SpO2 levels and hypoxia-induced lowered executive function is still unclear. Here we aimed to clarify whether hypoxia-induced lowered executive function was associated with arterial oxygen desaturation, using 21 participants performing the color-word Stroop task under normoxic and three hypoxic conditions (FIO2  = 0...
March 13, 2018: Journal of Physiological Sciences: JPS
Yousef Zakharia, Arup Bhattacharya, Youcef M Rustum
Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent...
February 13, 2018: Oncotarget
Tomohiro Katagiri, Minoru Kobayashi, Michio Yoshimura, Akiyo Morinibu, Satoshi Itasaka, Masahiro Hiraoka, Hiroshi Harada
Hypoxic and stroma-rich microenvironments, characteristic features of pancreatic cancers, are strongly associated with a poor prognosis. However, whether and how hypoxia increases stromal compartments remain largely unknown. Here, we investigated the potential importance of a master regulator of the cellular adaptive response to hypoxia, hypoxia-inducible factor-1 (HIF-1), in the formation of stroma-rich microenvironments of pancreatic tumors. We found that pancreatic cancer cells secreted more Sonic hedgehog protein (SHH) under hypoxia by upregulating its expression and efficiency of secretion in a HIF-1-dependent manner...
February 13, 2018: Oncotarget
Liya Pi, Chunhua Fu, Yuanquing Lu, Junmei Zhou, Marda Jorgensen, Vinayak Shenoy, Kenneth E Lipson, Edward W Scott, Andrew J Bryant
Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown...
2018: Frontiers in Physiology
Peng Jin, Seung-Hyun Shin, Yang-Sook Chun, Hyun-Woo Shin, Yong Jae Shin, Yeri Lee, Donggeon Kim, Do-Hyun Nam, Jong-Wan Park
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells...
March 14, 2018: Oncogene
Ying Pang, Garima Gupta, Chunzhang Yang, Herui Wang, Thanh-Truc Huynh, Ziedulla Abdullaev, Svetlana D Pack, Melanie J Percy, Terence R J Lappin, Zhengping Zhuang, Karel Pacak
BACKGROUND: The role of the hypoxia signaling pathway in the pathogenesis of pheochromocytoma/paraganglioma (PPGL)-polycythemia syndrome has been elucidated. Novel somatic mutations in hypoxia-inducible factor type 2A (HIF2A) and germline mutations in prolyl hydroxylase type 1 and type 2 (PHD1 and PHD2) have been identified to cause upregulation of the hypoxia signaling pathway and its target genes including erythropoietin (EPO) and its receptor (EPOR). However, in a minority of patients presenting with this syndrome, the genetics and molecular pathogenesis remain unexplained...
March 13, 2018: BMC Cancer
Monica Currò, Tiziana Russo, Nadia Ferlazzo, Daniela Caccamo, Pietro Antonuccio, Salvatore Arena, Saveria Parisi, Patrizia Perrone, Riccardo Ientile, Carmelo Romeo, Pietro Impellizzeri
Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE® ) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE® cream for 7 days before circumcision...
March 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Liwei Xie, Amelia Yin, Anna S Nichenko, Aaron M Beedle, Jarrod A Call, Hang Yin
The remarkable regeneration capability of skeletal muscle depends on coordinated proliferation and differentiation of satellite cells. The self-renewal of satellite cells is critical for long-term maintenance of muscle regeneration potential. Hypoxia profoundly affects the proliferation, differentiation, and self-renewal of cultured myoblasts. However, the physiological relevance of hypoxia and hypoxia signaling in satellite cells in vivo remains largely unknown. Here, we report that satellite cells are in an intrinsic hypoxic state in vivo and express hypoxia-inducible factor 2A (HIF2A)...
March 13, 2018: Journal of Clinical Investigation
Qixiang Zhao, Zhiwei Liu, Bing Huang, Yanliang Yuan, Xiucheng Liu, Hu Zhang, Fan Qiu, Yiqian Zhang, Yufeng Li, Haoran Miao, Hongyan Dong, Zhongming Zhang
The prevention and management of myocardial ischemia/reperfusion (MI/R) injury is an essential part of coronary heart disease surgery and is becoming a major clinical problem in the treatment of ischemic heart disease. Previous studies by our group have demonstrated that pigment epithelium‑derived factor (PEDF) improves cardiac function in rats with acute myocardial infarction and reduces hypoxia‑induced cell injury. However, the protective function and mechanisms underlying the effect of PEDF in MI/R injury remain to be fully understood...
March 9, 2018: International Journal of Molecular Medicine
Jeffrey D Bryant, Michael C Brown, Mikhail I Dobrikov, Elena Y Dobrikova, Sarah L Gemberling, Qing Zhang, Matthias Gromeier
Death associated protein 5 (DAP5) is an atypical isoform of the translation initiation scaffolds eukaryotic initiation factors 4GI and II (eIF4GI/II), which recruit mRNAs to ribosomes in mammals. Unlike eIF4GI/II, DAP5 binds eIF2β, a subunit of the eIF2 complex that delivers methionyl-tRNA to ribosomes. We discovered that DAP5:eIF2β binding depends on specific stimuli, e.g. protein kinase C (PKC)-Raf-ERK1/2 signals, and determines DAP5's influence on global and template-specific translation. DAP5 depletion caused an unanticipated surge of hypoxia-inducible factor 1α (HIF-1α), the transcription factor and master switch of the hypoxia response...
March 12, 2018: Molecular and Cellular Biology
Guolei Zhang, Junpu Zha, Junchuan Liu, Jun Di
One of the crucial mechanisms following spinal cord injury is mitochondria associated cell death. Minocycline, an anti-inflammatory drug is well known to impede the mitochondrial cell death. However, there has been no study on the effect of minocycline linking FAS-mediated cell death and hypoxia inducible factor (HIF-1α), the targets involved in mitochondrial cell death. Male Sprague Drawley rats (N = 18, divided into three groups) were subjected to traumatic spinal cord injury and were injected with minocycline (n = 6) (90 mg/kg, and later 45 mg/kg dose two times a day (every 12 h)...
March 9, 2018: Microbial Pathogenesis
Antonella Cotoia, Lucia Mirabella, Sabrina Altamura, Rachele Villani, Flavia Marchese, Giuseppe Ferrara, Karim Mariano, Tullo Livio, Gilda Cinnella
BACKGROUND: Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments...
March 12, 2018: Trials
Iglika G Ivanova, Catherine V Park, Adrian I Yemm, Niall S Kenneth
HIF1α (hypoxia inducible factor 1α) is the central regulator of the cellular response to low oxygen and its activity is deregulated in multiple human pathologies. Consequently, given the importance of HIF signaling in disease, there is considerable interest in developing strategies to modulate HIF1α activity and down-stream signaling events. In the present study we find that under hypoxic conditions, activation of the PERK branch of the unfolded protein response (UPR) can suppress the levels and activity of HIF1α by preventing efficient HIF1α translation...
February 26, 2018: Nucleic Acids Research
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