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https://www.readbyqxmd.com/read/29791781/a-dual-role-of-mir-22-in-rhabdomyolysis-induced-acute-kidney-injury-aki
#1
Susanne Mathia, Lucas J Rudigier, Mumtaz Kasim, Karin M Kirschner, Pontus B Persson, Kai-Uwe Eckardt, Christian Rosenberger, Michael Fähling
AIM: In acute kidney injury (AKI) regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia inducible factor (HIF) is limited. Here we studied miR-22, a potential HIF repressor, in normal kidneys, as well as in rhabdomyolysis-induced AKI, a condition where miR-22 is up-regulated. METHODS: AKI in mice was provoked by IM injection of glycerol. Tissue homogenates were processed to determine the levels of candidate RNAs and proteins, as well as global gene expression profiles...
May 23, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29786753/hypoxia%C3%A2-induced-expression-of-cxcr4-favors-trophoblast-cell-migration-and-invasion-via-the-activation-of-hif%C3%A2-1%C3%AE
#2
Zhan Zhang, Pengyun Li, Yan Wang, Huan Yan
The placenta initially develops in a low‑oxygen environment up to week 8‑10 of gestation, and a low oxygen level is a critical factor in the regulation of trophoblast migration and invasion. CXC chemokine receptor 4 (CXCR4) is transcriptionally activated by hypoxia in cancer cells. However, whether CXCR4 is involved in hypoxia‑inducible factor (HIF)‑1α‑dependent trophoblastic migration and invasion in a physiologically hypoxic environment (3% O2) remains to be fully elucidated and requires further investigation...
May 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29785943/-roles-and-molecular-mechanisms-of-hypoxia-inducible-factors-in-renal-cell-carcinoma
#3
Jun Xia Zou, Ke Chen
Renal cancer is a common urologic malignancy. However, the therapeutic options for metastatic renal cancer patients are limited. Hypoxia (low oxygen) is a fundamental microenvironmental determinant of solid tumor pathophysiology. Recent data from molecular and clinical studies indicate that hypoxia-inducible factors (HIFs) play critical roles in the development and progress of renal cell carcinoma (RCC). The HIF transcription factor family is a type of heterodimeric transcription factor consisting of HIF-α and HIF-β subunits and can transcriptionally activate genes that mediate the hypoxic response...
May 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29780805/stabilization-of-hypoxia-inducible-factor-1-alpha-augments-the-therapeutic-capacity-of-bone-marrow-derived-mesenchymal-stem-cells-in-experimental-pneumonia
#4
Naveen Gupta, Victor Nizet
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29779471/hypoxia-induces-hypoxia-inducible-factor-1%C3%AE-and-potential-hif-responsive-gene-expression-in-uterine-leiomyoma
#5
Hiroshi Ishikawa, Linlin Xu, Kunizui Sone, Tatsuya Kobayashi, Guiwen Wang, Makio Shozu
Uterine leiomyoma is characterized by abundant extracellular matrix and broad avascular areas, both constantly resulting in hypoxia, suggesting some hypoxia-induced response function. Here, we examined whether hypoxia-inducible factor 1α (HIF-1α)- mediated hypoxic response function in uterine leiomyoma. Immunoblotting detected higher basal HIF-1α protein expression in nuclear extracts from uterine leiomyoma tissues than in those from the adjacent myometrium ( P = .0011). Immunohistochemical analysis revealed the presence of HIF-1α-positive cellular components in both leiomyoma and surrounding myometrial tissues...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29755367/the-transcription-factor-hif-1-enhances-the-radio-resistance-of-mouse-mscs
#6
Irene Calvo-Asensio, Eugène T Dillon, Noel F Lowndes, Rhodri Ceredig
Mesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSCs have an efficient DNA damage response (DDR) and are consequently relatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif-1 is involved in mouse MSC radio-resistance, however its exact mechanism of action remains unknown...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29753689/molecular-characterization-and-gene-expression-analysis-of-hypoxia-inducible-factor-and-its-inhibitory-factors-in-kuruma-shrimp-marsupenaeus-japonicus
#7
Yo Okamura, Tohru Mekata, Gehad Elsaid Elshopakey, Toshiaki Itami
In shrimp aquaculture, overcrowded farming causes fluctuations in dissolved oxygen concentrations. Low-oxygen conditions (hypoxia) affect shrimp growth. Hypoxia-inducible factor (HIF) is a transcriptional factor in the basic helix-loop-helix/PAS family and is activated in response to hypoxic stress. However, little is known about HIF and other inhibitors of the HIF pathway in crustaceans. In this study, we cloned MjHIF-1α, an inhibitory factor, MjFIH-1 (factor inhibiting HIF-1α), and MjVHL (Von Hippel-Lindau tumor suppressor) from kuruma shrimp (Marsupenaeus japonicus)...
May 10, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29750308/actinidia-chinensis-planch-polysaccharide-protects-against-hypoxia%C3%A2-induced-apoptosis-of-cardiomyocytes-in-vitro
#8
Qiang Wang, Yunfa Xu, Ying Gao, Qi Wang
Cardiac hypertrophy is frequently accompanied by ischemic heart disease. Actinidia chinensis planch polysaccharide (ACP) is the main active compound from Actinidia chinensis planch. In the present study, a cardiac hypertrophy model was produced by treating cells with Angiotensin II (Ang II), which was used to investigate whether ACP protected against cardiac hypertrophy in vitro. It was demonstrated that ACP alleviated Ang II‑induced cardiac hypertrophy. In addition, pretreatment with ACP prior to hypoxic culture reduced the disruption of the mitochondrial membrane potential as investigated by flow cytometry...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29749460/role-of-txndc5-in-tumorigenesis-of-colorectal-cancer-cells-in-vivo-and-in-vitro-evidence
#9
Fengbo Tan, Hong Zhu, Xiao He, Nanhui Yu, Xingwen Zhang, Haifan Xu, Haiping Pei
Thioredoxin domain‑containing 5 (TXNDC5) is reportedly overexpressed in colorectal cancer (CRC) and is therefore considered an oncogene. However, the role of TXNDC5 in CRC tumorigenesis remains unclear. The present study aimed to explore the role of TXNDC5 in CRC tumorigenesis in vitro and in vivo under hypoxic and normoxic conditions. Analyses of patient tissue samples revealed a positive association between the expression of hypoxia‑inducible factor‑1α (HIF‑1α) or TXNDC5 and the TNM stage of CRC...
May 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29746587/metabolic-reprogramming-of-kaposi-s-sarcoma-associated-herpes-virus-infected-b-cells-in-hypoxia
#10
Rajnish Kumar Singh, Fengchao Lang, Yonggang Pei, Hem Chandra Jha, Erle S Robertson
Kaposi's sarcoma associated herpesvirus (KSHV) infection stabilizes hypoxia inducible factors (HIFs). The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency, reactivation and associated disease phenotypes. Besides modulation of large-scale signaling, KSHV infection also reprograms the metabolic activity of infected cells. However, the mechanism and cellular pathways modulated during these changes are poorly understood. We performed comparative RNA sequencing analysis on cells with stabilized hypoxia inducible factor 1 alpha (HIF1α) of KSHV negative or positive background to identify changes in global and metabolic gene expression...
May 10, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29742498/fg-4592-accelerates-cutaneous-wound-healing-by-epidermal-stem-cell-activation-via-hif-1%C3%AE-stabilization
#11
Di Tang, Junhui Zhang, Tiantian Yan, Jingyu Wei, Xupin Jiang, Dongxia Zhang, Qiong Zhang, Jiezhi Jia, Yuesheng Huang
BACKGROUND/AIMS: Regional hypoxia promptly develops after trauma because of microvascular injury and increased oxygen consumption. This acute hypoxia plays a positive role in early skin wound healing. One of the mechanisms underlying the beneficial effects of acute hypoxia on wound healing may be increased hypoxia-inducible factor-1 (HIF-1α) expression. HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling...
May 5, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29740424/modulation-of-dengue-zika-virus-pathogenicity-by-antibody-dependent-enhancement-and-strategies-to-protect-against-enhancement-in-zika-virus-infection
#12
REVIEW
Rekha Khandia, Ashok Munjal, Kuldeep Dhama, Kumaragurubaran Karthik, Ruchi Tiwari, Yashpal Singh Malik, Raj Kumar Singh, Wanpen Chaicumpa
Antibody-dependent enhancement (ADE) is a phenomenon in which preexisting poorly neutralizing antibodies leads to enhanced infection. It is a serious concern with mosquito-borne flaviviruses such as Dengue virus (DENV) and Zika virus (ZIKV). In vitro experimental evidences have indicated the preventive, as well as a pathogenicity-enhancing role, of preexisting DENV antibodies in ZIKV infections. ADE has been confirmed in DENV but not ZIKV infections. Principally, the Fc region of the anti-DENV antibody binds with the fragment crystallizable gamma receptor (FcγR), and subsequent C1q interactions and immune effector functions are responsible for the ADE...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29739381/angiopoietin-like-4-promotes-osteosarcoma-cell-proliferation-and-migration-and-stimulates-osteoclastogenesis
#13
T Zhang, A Kastrenopoulou, Q Larrouture, N A Athanasou, H J Knowles
BACKGROUND: Osteosarcoma is the most common primary bone cancer in children and young adults. It is highly aggressive and patients that present with metastasis have a poor prognosis. Angiopoietin-like 4 (ANGPTL4) drives the progression and metastasis of many solid tumours, but has not been described in osteosarcoma tissue. ANGPTL4 also enhances osteoclast activity, which is required for osteosarcoma growth in bone. We therefore investigated the expression and function of ANGPTL4 in human osteosarcoma tissue and cell lines...
May 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29738851/intranasally-delivered-small-interfering-rna-mediated-suppression-of-scavenger-receptor-mac-1-attenuates-microglial-phenotype-switching-and-working-memory-impairment-following-hypoxia
#14
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29735668/modeling-combination-therapy-for-breast-cancer-with-bet-and-immune-checkpoint-inhibitors
#15
Xiulan Lai, Andrew Stiff, Megan Duggan, Robert Wesolowski, William E Carson, Avner Friedman
CTLA-4 is an immune checkpoint expressed on active anticancer T cells. When it combines with its ligand B7 on dendritic cells, it inhibits the activity of the T cells. The Bromo- and Extra-Terminal (BET) protein family includes proteins that regulate the expression of key oncogenes and antiapoptotic proteins. BET inhibitor (BETi) has been shown to reduce the expression of MYC by suppressing its transcription factors and to down-regulate the hypoxic transcriptome response to VEGF-A. This paper develops a mathematical model of the treatment of cancer by combination therapy of BETi and CTLA-4 inhibitor...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29731878/conversion-of-epithelial-to-mesenchymal-transition-to-mesenchymal-to-epithelial-transition-is-mediated-by-oxygen-concentration-in-pancreatic-cancer-cells
#16
Shuo Chen, Xi Chen, Wei Li, Tao Shan, Wan Run Lin, Jiancang Ma, Xijuan Cui, Wenbin Yang, Gang Cao, Yiming Li, Li Wang, Ya'an Kang
Tumor metastasis is accompanied by a two-stage process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Currently, the exact mechanisms underlying EMT-MET conversion are unclear. In the present study, the mechanisms by which primary sites (hypoxic) and homing sites (normoxic or hyperoxic) participate in EMT-MET conversion were evaluated. Pancreatic cancer cells were grown under different oxygenation conditions. Cell morphology and epithelial (E)-cadherin and vimentin expression were examined...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29721585/lon-in-maintaining-mitochondrial-and-endoplasmic-reticulum-homeostasis
#17
REVIEW
Jieyeqi Yang, Wenying Chen, Boyang Zhang, Fengli Tian, Zheng Zhou, Xin Liao, Chen Li, Yi Zhang, Yanyan Han, Yan Wang, Yuzhe Li, Guo-Qing Wang, Xiao Li Shen
As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc...
May 2, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29719086/overexpression-of-genes-associated-with-hypoxia-in-cattle-adapted-to-trans-himalayan-region-of-ladakh
#18
Preeti Verma, Ankita Sharma, Monika Sodhi, Kiran Thakur, Vijay Bharti, Prabhat Kumar, Arup Giri, Sahil Kalia, Shelesh Kumar Swami, Manishi Mukesh
Ladakh is an important part of the Trans-Himalayan region located between the Kunlun mountain range in the north and the main Great Himalayas to the south in the state of Jammu and Kashmir of India. The local cattle from Leh and Ladakh region, known as "Ladakhi cattle" is a unique germplasm having excellent adaptation potential to high altitude hypobaric stress. In the present study, an effort was made to evaluate the transcriptional pattern of hypoxia inducing factor-1 (HIF-1) and several of its regulated genes in PBMCs of local Ladakhi cattle, Holstein Frisian crosses, Jersey (exotic) maintained at high altitude region and Sahiwal (Bos indicus) and Karan Fries (cross bred) cattle maintained in tropical environment...
May 2, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29717634/notch-signaling-enhances-stemness-by-regulating-metabolic-pathways-through-modifying-p53-nf-%C3%AE%C2%BAb-and-hif-1%C3%AE
#19
Hiroyuki Moriyama, Mariko Moriyama, Toshiyuki Ozawa, Daisuke Tsuruta, Taro Iguchi, Satoshi Tamada, Tatsuya Nakatani, Koichi Nakagawa, Takao Hayakawa
Human adipose-derived stromal cells (hASCs) are attractive for regenerative medicine, but their limited in vitro lifespan limits their therapeutic applicability. Recent data demonstrate that hypoxia may benefit the ex vivo culture of stem cells. Such cells exhibit a high level of glycolytic metabolism under hypoxic conditions. However, the physiological role of glycolytic activation and its underlying regulatory mechanism are incompletely understood. We have shown that when activated under conditions of 5% O<sub>2</sub>, Notch signaling dramatically increases the rate of glycolysis, improves proliferation efficiency, prevents senescence, and maintains the multipotency of hASCs...
May 2, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29717265/identification-of-a-met-eif4g1-translational-regulation-axis-that-controls-hif-1%C3%AE-levels-under-hypoxia
#20
Astrid A Glück, Eleonora Orlando, Dominic Leiser, Michaela Poliaková, Lluís Nisa, Aurélie Quintin, Jacopo Gavini, Deborah M Stroka, Sabina Berezowska, Lukas Bubendorf, Andree Blaukat, Daniel M Aebersold, Michaela Medová, Yitzhak Zimmer
Poor oxygenation is a common hallmark of solid cancers that strongly associates with aggressive tumor progression and treatment resistance. While a hypoxia-inducible factor 1α (HIF-1α)-associated transcriptional overexpression of the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) MET has been previously documented, any regulation of the HIF-1α system through MET downstream signaling in hypoxic tumors has not been yet described. By using MET-driven in vitro as well as ex vivo tumor organotypic fresh tissue models we report that MET targeting results in depletion of HIF-1α and its various downstream targets...
May 2, 2018: Oncogene
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