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Guest Editor

School of Pharmacy and Bioengineering, Keele University, Keele ST5 5BJ, UK
Interests: hypoxia inducible factors; stroke; neuroprotection; blood brain barrier; Vascular dementia; neuroinflammation; cerebrospinal fluid

Prof. Dr. Nicholas R. Forsyth

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Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent ST4 7QB, UK
Interests: regenerative medicine; tissue engineering; hypoxia; adult stem cells; pluripotent stem cells; tendon; cartilage; respiratory system; 3D culture

Prof. Dr. Christopher J. Schofield

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Guest Editor

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK
Interests: synthetic chemistry; 2-oxoglutarate oxygenase; oxygen sensing; hypoxia; epigenetics; demethylases; DNA repair; obesity; antibiotic biosynthesis; flavonoid and ethylene biosynthesis

Special Issue Information

Dear Colleagues,

Since the discovery of hypoxia inducible factors (HIF), the research on medical applications of HIF stabilizers/inhibitors has been growing at an exponential rate. The 2019 Nobel Prize in Physiology or Medicine went to the hypoxia researchers that discovered how cells sense and adapt to hypoxia. Low O₂ tension (hypoxia) is mainly related to pathological situations, but it can also be a part of normal physiology. Hypoxia activates the hypoxia signaling pathway, which is predominately governed by HIF. HIF stabilization upregulates hundreds of human genes, which are related to metabolism, erythropoietin, angiogenesis, proliferation, and survival. On the other hand, HIF is engaged in the pathology of disease. Modulating the hypoxia signaling pathway, thus altering gene expression in diseases, can be used to treat these diseases, e.g., anemia, ischemic diseases, cancer. In this Special Issue, several of these aspects in hypoxia signaling modulation will be highlighted. We invite the submission of research papers that will consolidate our understanding in this area. Contributions to this Special Issue are invited in the form of reviews, research articles, communications, and concept papers.

Areas to be covered in this Special Issue may include but are not limited to:

Hypoxia signaling in normal function;
Hypoxia signaling in diseases;
Hypoxia signaling in therapeutic targets;
Development of hypoxia mimetic agents for clinical uses.

Dr. Ruoli Chen
Dr. Nicholas R. Forsyth
Prof. Christopher J. Schofield
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2300 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Hypoxia
Hypoxia inducible facor
stablizer
inhibitor

Published Papers (2 papers)

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Research

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Open AccessArticle

Dimethyloxalylglycine (DMOG), a Hypoxia Mimetic Agent, Does Not Replicate a Rat Pheochromocytoma (PC12) Cell Biological Response to Reduced Oxygen Culture

RuoLi Chen

Mohammad Alkataan Ahmed

and

Nicholas Robert Forsyth

Biomolecules 2022, 12(4), 541; https://doi.org/10.3390/biom12040541 - 03 Apr 2022

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Abstract

Cells respond to reduced oxygen availability predominately by activation of the hypoxia-inducible factor (HIF) pathway. HIF activation upregulates hundreds of genes that help cells survive in the reduced oxygen environment. The aim of this study is to determine whether chemical-induced HIF accumulation mimics all aspects of the hypoxic response of cells. We compared the effects of dimethyloxalylglycine (DMOG) (a HIF stabiliser) on PC12 cells cultured in air oxygen (20.9% O_2, AO) with those cultured in either intermittent 20.9% O₂ to 2% O₂ (IH) or constant 2% O₂ (CN). Cell viability, cell cycle, HIF accumulation, reactive oxygen species (ROS) formation, mitochondrial function and differentiation were used to characterise the PC12 cells and evaluate the impact of DMOG. IH and CN culture reduced the increase in cell numbers after 72 and 96 h and MTT activity after 48 h compared to AO culture. Further, DMOG supplementation in AO induced a dose-dependent reduction in the increase in PC12 cell numbers and MTT activity. IH-cultured PC12 cells displayed increased and sustained HIF-1 expression over 96 h. This was accompanied by increased ROS and mitochondrial burden. PC12 cells in CN displayed little changes in HIF-1 expression or ROS levels. DMOG (0.1 mM) supplementation resulted in an IH-like HIF-1 profile. The mitochondrial burden and action potential of DMOG-supplemented PC12 cells did not mirror those seen in other conditions. DMOG significantly increased S phase cell populations after 72 and 96 h. No significant effect on PC12 cell differentiation was noted with IH and CN culture without induction by nerve growth factor (NGF), while DMOG significantly increased PC12 cell differentiation with and without NGF. In conclusion, DMOG and reduced oxygen levels stabilise HIF and affect mitochondrial activity and cell behaviour. However, DMOG does not provide an accurate replication of the reduced oxygen environments. Full article

(This article belongs to the Special Issue State-of-the-Art Modulating Hypoxia Signaling Pathway to Treat Human Diseases)

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Review

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Open AccessReview

Targeting Hypoxia: Revival of Old Remedies

Nuria Vilaplana-Lopera

Maxym Besh

and

Eui Jung Moon

Biomolecules 2021, 11(11), 1604; https://doi.org/10.3390/biom11111604 - 29 Oct 2021

Cited by 5 | Viewed by 2213

Abstract

Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. Despite the accumulative scientific and clinical efforts to target hypoxia, there is still a need to find specific treatments for tumour hypoxia. In this review, we discuss a variety of approaches to alter the low oxygen tumour microenvironment or hypoxia pathways including carbogen breathing, hyperthermia, hypoxia-activated prodrugs, tumour metabolism and hypoxia-inducible factor (HIF) inhibitors. The recent advances in technology and biological understanding reveal the importance of revisiting old therapeutic regimens and repurposing their uses clinically. Full article

(This article belongs to the Special Issue State-of-the-Art Modulating Hypoxia Signaling Pathway to Treat Human Diseases)

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