Review
Biochemistry & Molecular Biology
Diego Rodriguez, Deepika Watts, Diana Gaete, Sundary Sormendi, Ben Wielockx
Summary: The vascular network is crucial for sensing oxygen levels and hypoxia triggers a cascade of cellular signals, including angiogenesis, regulated by transcription factors such as HIFs and oxygen sensors like PHDs. Understanding how vascular cells respond to hypoxia under varying conditions is important for potential therapeutic targets in vascular dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Ilias Mylonis, Georgia Chachami, George Simos
Summary: Hypoxia inducible transcription factors (HIFs) play a critical role in enabling cancer cells to thrive in low oxygen conditions. Inhibiting HIFs can prevent cancer cell growth and metastasis, with peptide HIF inhibitors showing potential as highly selective therapeutic agents. This review highlights the importance of targeting HIFs in cancer treatment and the promising development of peptide inhibitors.
Review
Biochemistry & Molecular Biology
Marta Domenech, Ainhoa Hernandez, Andrea Plaja, Eva Martinez-Balibrea, Carmen Balana
Summary: Glioblastoma is the most aggressive form of brain tumor in adults, with hypoxia-induced factor 1 (HIF-1) serving as an important driver of tumor progression by promoting angiogenesis, immunosuppression, and metabolic reprogramming. HIF-1 is not only regulated by oxygen levels but also by various oncogenic signaling pathways, and inhibiting the hypoxia pathway could be a crucial treatment alternative for GB patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Kiichi Hirota
Summary: Oxygen is essential for the body, with the hypoxia-inducible factor playing a key role in hypoxic environments. HIF-prolyl hydroxylases serve as oxygen sensors, detecting decreases in oxygen partial pressure. Inhibiting HIF-PH can activate HIF artificially for medical intervention purposes.
Review
Oncology
Diana Gaete, Diego Rodriguez, Deepika Watts, Sundary Sormendi, Triantafyllos Chavakis, Ben Wielockx
Summary: Solid tumors often face hypoxic environments, leading to activation of HIFs and subsequent regulation by PHDs to counteract internal stress. PHDs have the potential to be a therapeutic target in anti-tumor treatments.
Article
Gastroenterology & Hepatology
Peter A. C. Wing, Peter Jianrui Liu, James M. Harris, Andrea Magri, Thomas Michler, Xiaodong Zhuang, Helene Borrmann, Rosalba Minisini, Nicholas R. Frampton, Jochen M. Wettengel, Laurent Mailly, Valentina D'Arienzo, Tobias Riedl, Luis Nobre, Michael P. Weekes, Mario Pirisi, Mathias Heikenwalder, Thomas F. Baumert, Ester M. Hammond, David R. Mole, Ulrike Protzer, Peter Balfe, Jane A. McKeating
Summary: HIFs play a crucial role in regulating HBV replication, revealing an evolutionary mechanism by which HBV exploits the HIF signaling pathway to persist in the low oxygen environment of the liver.
JOURNAL OF HEPATOLOGY
(2021)
Article
Cell Biology
Ines Godet, Steven Doctorman, Fan Wu, Daniele M. Gilkes
Summary: The rapid proliferation of cancer cells and hypoxia cause regions of nutrient and oxygen deprivation in solid tumors. Some cancer cells can adapt to hypoxic conditions and promote cancer progression. Hypoxia is associated with worse patient prognosis, highlighting the need for methods to measure oxygen concentrations. This review provides an overview of the main methods utilized to detect hypoxia in cancer cells.
Article
Biochemistry & Molecular Biology
Zhilong Ren, Duilio Michele Potenza, Yiqiong Ma, Guillaume Ajalbert, David Hoogewijs, Xiu-Fen Ming, Zhihong Yang
Summary: Hypoxia causes injury to podocytes, and the presence of Arg-II in podocytes contributes to this injury. However, the elimination of Arg-II does not significantly affect hypoxia-induced albuminuria, but it does reduce albuminuria in aging.
Article
Biochemistry & Molecular Biology
Daniela Mennerich, Kateryna Kubaichuk, Ghulam S. Raza, Dominik C. Fuhrmann, Karl-Heinz Herzig, Bernhard Bruene, Thomas Kietzmann
Summary: Metabolic adaptation and signal integration in response to hypoxia is regulated by hypoxia-inducible factors (HIFs). This study shows that high fat diet-induced endoplasmic reticulum stress attenuates the response to hypoxia by promoting the degradation of HIF-1 and HIF-2 through GSK3 beta and the ubiquitin ligase FBXW1A/beta TrCP, leading to decreased proliferation, migration, and increased sensitivity to ER stress-induced apoptosis. Moreover, hypoxia affects the ER stress response mainly through the PERK-arm of the unfolded protein response (UPR).
Review
Pharmacology & Pharmacy
Xinguo Jiang, Wen Tian, Dongeon Kim, Alexander S. McQuiston, Ryan Vinh, Stanley G. Rockson, Gregg L. Semenza, Mark R. Nicolls
Summary: Lymphedema is a chronic inflammatory disorder with incomplete understanding of its pathology and lack of approved pharmacological therapy. Studying hypoxia-regulated pathways in lymphedema may lead to new treatment approaches.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Genetics & Heredity
Maciej Jaskiewicz, Adrianna Moszynska, Magdalena Gebert, James F. Collawn, Rafal Bartoszewski
Summary: Cellular adaptation to hypoxia is regulated by hypoxia inducible factors HIF-1 and HIF-2. HIF-1 mediates acute hypoxia response, while HIF-2 allows adaptation to chronic oxygen deprivation. Transition from HIF-1 to HIF-2 during hypoxia is possible due to the low stability of HIF-1 alpha subunit transcript (HIF1A) and the stable mRNA of HIF-2 alpha (EPAS1). However, no microRNAs (miRNAs) have been found to regulate endothelial HIF-2 levels during hypoxia.
Review
Biochemistry & Molecular Biology
Thuy-Hang Nguyen, Stephanie Conotte, Alexandra Belayew, Anne-Emilie Decleves, Alexandre Legrand, Alexandra Tassin
Summary: Muscular dystrophies are genetic degenerative muscle disorders characterized by muscle wasting, often accompanied by respiratory impairments and hypoxemia. Hypoxic stress activates compensatory mechanisms, with HIF-1α playing a key role. Alterations in HIF-1α in muscle may impact the pathophysiology of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
S. J. Kierans, C. T. Taylor
Summary: Under hypoxic conditions, eukaryotic cells can shift metabolism towards glycolysis to maintain ATP levels, a process regulated by HIF-1 alpha. This metabolic switch is crucial for cellular survival during acute hypoxic stress and has implications for cancer cell survival and growth. Understanding the mechanisms central to this reprogramming is important for both physiological and pathophysiological processes.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Virology
David A. Davis, Prabha Shrestha, Robert Yarchoan
Summary: The complex interactions between Kaposi sarcoma-associated herpesvirus (KSHV), hypoxia, and hypoxia-inducible factors (HIFs) play important roles in the pathogenesis of KSHV-induced diseases. Interfering with HIFs can decrease tumor growth and induce death of infected cells and KSHV-induced tumors, providing novel strategies for the treatment of KSHV-induced diseases.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Cell Biology
Nasim Kheshtchin, Jamshid Hadjati
Summary: Hypoxia, a common characteristic of solid tumors, contributes to different aspects of tumor progression and limits the efficacy of immunotherapies. Developing new immunotherapy strategies involving therapeutic targeting of HIF-1 molecules associated with hypoxia may enhance the clinical effectiveness of immunotherapy. Targeting hypoxia presents a potential opportunity to improve the clinical benefit of cancer immunotherapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Editorial Material
Biochemical Research Methods
Jason R. Swedlow, Pasi Kankaanpaa, Ugis Sarkans, Wojtek Goscinski, Graham Galloway, Leonel Malacrida, Ryan P. Sullivan, Steffen Hartel, Claire M. Brown, Christopher Wood, Antje Keppler, Federica Paina, Ben Loos, Sara Zullino, Dario Livio Longo, Silvio Aime, Shuichi Onami
Summary: Imaging technologies play a crucial role in understanding biological mechanisms and in diagnosis and therapy in animal and human medicine. Establishing globally applicable guidelines for open image data tools and resources can help advance the rapidly developing fields of biological and biomedical imaging.
Review
Biochemistry & Molecular Biology
Brian M. Ortmann, James A. Nathan
Summary: Organisms have evolved oxygen-sensing mechanisms to adapt to oxygen availability; HIFs play a crucial role in oxygen-sensing in metazoans; Genetic studies have contributed significantly to our understanding of oxygen-sensing pathways.
Article
Genetics & Heredity
Brian M. Ortmann, Natalie Burrows, Ian T. Lobb, Esther Arnaiz, Niek Wit, Peter S. J. Bailey, Louise H. Jordon, Olivia Lombardi, Ana Penalver, James McCaffrey, Rachel Seear, David R. Mole, Peter J. Ratcliffe, Patrick H. Maxwell, James A. Nathan
Summary: The histone H3K4 methyltransferase SET1B plays a crucial role in the transcriptional activity of HIF target genes, and its loss results in impaired cell growth and tumor formation. Experimental findings demonstrate that SET1B accumulates on chromatin in hypoxia and is recruited to HIF target genes by the HIF complex.
Editorial Material
Biochemical Research Methods
Ulrike Boehm, Glyn Nelson, Claire M. Brown, Steve Bagley, Peter Bajcsy, Johanna Bischof, Aurelien Dauphin, Ian M. Dobbie, John E. Eriksson, Orestis Faklaris, Julia Fernandez-Rodriguez, Alexia Ferrand, Laurent Gelman, Ali Gheisari, Hella Hartmann, Christian Kukat, Alex Laude, Miso Mitkovski, Sebastian Munck, Alison J. North, Tobias M. Rasse, Ute Resch-Genger, Lucas C. Schuetz, Arne Seitz, Caterina Strambio-De-Castillia, Jason R. Swedlow, Roland Nitschke
Summary: The initiative QUAREP-LiMi aims to improve reproducibility of light microscopy image data by implementing quality control management of instruments and images, with a focus on establishing a common set of QC guidelines for hardware calibration and image acquisition, management, and analysis.
Article
Obstetrics & Gynecology
Franz S. Gruber, Zoe C. Johnston, Neil R. Norcross, Irene Georgiou, Caroline Wilson, Kevin D. Read, Ian H. Gilbert, Jason R. Swedlow, Sarah Martins da Silva, Christopher L. R. Barratt
Summary: This study utilized a high-throughput screening platform to identify compounds that can enhance sperm motility, providing a promising starting point for male fertility drug discovery.
HUMAN REPRODUCTION
(2022)
Editorial Material
Multidisciplinary Sciences
Jason R. Swedlow, Lucy Collinson
Editorial Material
Biotechnology & Applied Microbiology
Philip S. Jones, Steven van Helden, Volkhart Min-Jian Li, Ton Vries, Jon S. B. de Vlieger
Summary: The European Lead Factory combines assets and experience from major pharma with innovation and agility of academia and SMEs in a collaborative platform to expand access to high-throughput screening. With many successes heading towards the clinic, the organization is broadening its approach to screening and partnering.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Review
Developmental Biology
Zoe C. Johnston, Franz S. Gruber, Sean G. Brown, Neil R. Norcross, Jason Swedlow, Ian H. Gilbert, Christopher L. R. Barratt
Summary: Despite recent advances, there is still incomplete understanding of male infertility and male non-hormonal contraceptives. Direct observation of compounds' effects on sperm function can increase knowledge and advance the field.
Article
Multidisciplinary Sciences
Sara Carvalhal, Ingrid Bader, Martin A. Rooimans, Anneke B. Oostra, Jesper A. Balk, Rene G. Feichtinger, Christine Beichler, Michael R. Speicher, Johanna M. van Hagen, Quinten Waisfisz, Mieke van Haelst, Martijn Bruijn, Alexandra Tavares, Johannes A. Mayr, Rob M. F. Wolthuis, Raquel A. Oliveira, Job de Lange
Summary: BUB1 mutations cause neurodevelopmental disorder with cellular phenotypes similar to other syndromes.
Article
Medicine, General & Internal
Prasanti Kotagiri, Federica Mescia, Aimee L. Hanson, Lorinda Turner, Laura Bergamaschi, Ana Penalver, Nathan Richoz, Stephen D. Moore, Brian M. Ortmann, Benjamin J. Dunmore, Michael D. Morgan, Zewen Kelvin Tuong, Berthold Gottgens, Mark Toshner, Christoph Hess, Patrick H. Maxwell, Menna R. Clatworthy, James A. Nathan, John R. Bradley, Paul A. Lyons, Natalie Burrows, Kenneth G. C. Smith
Summary: Early and persistent defects in B cell subsets in COVID-19 are associated with hypoxia. Early oxygen therapy may be beneficial in correcting these immune deficiencies and improving outcomes.
Letter
Biochemical Research Methods
Xiaopeng Zhu, Yang Zhang, Yuchuan Wang, Dechao Tian, Andrew S. Belmont, Jason R. Swedlow, Jian Ma
Article
Multidisciplinary Sciences
Alexander J. Ropelewski, Megan A. Rizzo, Jason R. Swedlow, Jan Huisken, Pavel Osten, Neda Khanjani, Kurt Weiss, Vesselina Bakalov, Michelle Engle, Lauren Gridley, Michelle Krzyzanowski, Tom Madden, Deborah Maiese, Meisha Mandal, Justin Waterfield, David Williams, Carol M. Hamilton, Wayne Huggins
Summary: Recent advances in fluorescence microscopy techniques and tissue clearing, labeling, and staining have provided unprecedented opportunities for studying brain structure and function. Consistent annotation of metadata is crucial for understanding, reusing, and integrating these data.
Article
Biochemistry & Molecular Biology
Jarrod Shilts, Thomas W. M. Crozier, Ana M. Teixeira-Silva, Ildar M. Gabaev, Pehuen Pereyra Gerber, Edward J. D. Greenwood, Samuel James A. Watson, Brian M. Ortmann, Christian M. J. Gawden-Bone, Tekle J. Pauzaite, Markus J. Hoffmann, James A. Nathan, Stefan Pohlmann, Nicholas J. Matheson, Paul J. Lehner, Gavin J. Wright
Summary: In addition to ACE2, LRRC15 has been identified as a protein that interacts with the spike protein of SARS-CoV-2. The expression of LRRC15 is common in human lung vasculature cells and fibroblasts. Inflammatory signals greatly increase the levels of LRRC15 in the lungs of COVID-19 patients. Although LRRC15 alone is not sufficient for viral entry, it may modulate infection of human cells. Further investigation is needed to understand how SARS-CoV-2 exploits host LRRC15 and its role in COVID-19.
Article
Cell Biology
Xia Li, Dongmei Liu, Eric Griffis, Peter Novick
Summary: Bidirectional vesicular traffic is linked to both exocytic and endocytic pathways. Rab GTPases, including Sec4, are involved in determining the direction of vesicular transport. This study demonstrates that the directional specificity of Rab GTPase can be redirected, and that cells have a certain tolerance towards misdirection of Rab proteins.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Multidisciplinary Sciences
Linsey M. Porter, Wenrui Guo, Thomas WM. Crozier, Edward JD. Greenwood, Brian Ortmann, Daniel Kottmann, James A. Nathan, Ravindra Mahadeva, Paul J. Lehner, Frank McCaughan
Summary: The impact of cigarette smoke on ACE2 isoform expression and SARS-CoV-2 infection was investigated in this study. It was found that cigarette smoke did not significantly affect ACE2 expression or airway cell infection. Nicotine did not alter ACE2 expression, but NRF2 agonists did. These findings support the epidemiological data suggesting that smokers are not at increased risk of SARS-CoV-2 infection.
