Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases

Liao, Chengheng; Zhang, Qing

doi:10.1016/j.ajpath.2020.04.003

Cited by 36 publications

(27 citation statements)

References 110 publications

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“…Collagen P4Hs are considered to be attractive targets for drug inhibitors and involved in the treatment of fibrotic diseases and cancer metastasis (Vasta and Raines, 2018). Hypoxia-inducible transcription factor-prolyl 4-hydroxylase inhibitors are believed to have beneficial effects in the treatment of diseases such as myocardial infarction, stroke, peripheral vascular disease, diabetes, and severe anemias (Myllyharju, 2008;Liao and Zhang, 2020). ALKB homologs (ALKBH) homologs can regulate the physiological and pathological processes of cardiovascular diseases (CVDs), which have great potential in the development of CVD drugs and are expected to become a potential target for the treatment of CVD (Xiao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Zhou

Wang

et al. 2021

Front. Cell Dev. Biol.

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The 2-oxoglutarate/Fe (II)-dependent (2OG) oxygenase superfamily is mainly responsible for protein modification, nucleic acid repair and/or modification, and fatty acid metabolism and plays important roles in cancer, cardiovascular disease, and other diseases. They are likely to become new targets for the treatment of cancer and other diseases, so the accurate identification of 2OG oxygenases is of great significance. Many computational methods have been proposed to predict functional proteins to compensate for the time-consuming and expensive experimental identification. However, machine learning has not been applied to the study of 2OG oxygenases. In this study, we developed OGFE_RAAC, a prediction model to identify whether a protein is a 2OG oxygenase. To improve the performance of OGFE_RAAC, 673 amino acid reduction alphabets were used to determine the optimal feature representation scheme by recoding the protein sequence. The 10-fold cross-validation test showed that the accuracy of the model in identifying 2OG oxygenases is 91.04%. Besides, the independent dataset results also proved that the model has excellent generalization and robustness. It is expected to become an effective tool for the identification of 2OG oxygenases. With further research, we have also found that the function of 2OG oxygenases may be related to their polarity and hydrophobicity, which will help the follow-up study on the catalytic mechanism of 2OG oxygenases and the way they interact with the substrate. Based on the model we built, a user-friendly web server was established and can be friendly accessed at http://bioinfor.imu.edu.cn/ogferaac.

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Section: Introductionmentioning

confidence: 99%

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Zhou

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Vascular endothelial growth factor-A (VEGF-A) is a major proangiogenic factor driving angiogenesis. When the cells experience hypoxia, it stabilizes hypoxia inducible factor-1a (HIF-1a) (Lee et al, 2019;Yeo, 2019;Liao and Zhang, 2020). Stabilized HIF-1a translocates to the cell nucleus and forms a complex with HIF-1b, creating HIF-1 transcription factor.…”

Section: Introductionmentioning

confidence: 99%

“…Active HIF-1 signaling triggers the production of large number of angiogenic growth factors, among them VEGF. These soluble growth factors direct the sprouting of the new blood vessel, i.e., angiogenesis, to deliver oxygen and address the hypoxia in the tissue (Lee et al, 2019;Yeo, 2019;Liao and Zhang, 2020). VEGF also induces vascular permeability and leakage in ocular NV diseases (Ferrara et al, 2003;Penn et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

2020

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Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential anti-angiogenic factors for human diseases. We have recently performed the most comprehensive characterization of OIR by a relatively novel mass spectrometry (MS) technique, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS) proteomics and used genetically modified mice strains to identify novel molecular drug targets in angiogenic retinal diseases. We have confirmed the relevance of the identified molecular targets to human diseases by determining their expression pattern in neovascular membranes obtained from PDR and RVO patients. Based on our results, crystallins were the most prominent proteins induced by early hypoxic environment during the OIR, while actomyosin complex and Filamin A-R-Ras axis, that regulates vascular permeability of the angiogenic blood vessels, stood out at the peak of angiogenesis. Our results have revealed potential new therapeutic targets to address hypoxia-induced pathological angiogenesis and the associated vascular permeability in number of retinal diseases.

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“…In normoxic conditions, HIF-1α and HIF-2α can be hydroxylated by prolyl hydroxylases (PHDs). Hydroxylated α subunits are ubiquitinated by von Hippel Lindau E3 ubiquitin ligase ( VHL ) and consequently degraded by proteasomes [ 2 ]. Under hypoxic conditions, PHDs are inactivated due to the deficiency of oxygen.…”

Section: Introductionmentioning

confidence: 99%

“…Under hypoxic conditions, PHDs are inactivated due to the deficiency of oxygen. Therefore, the transcriptional activities of HIFs are promoted [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

Yun

Son

Choi

et al. 2021

IJMS

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Hypoxia-inducible factor-1 alpha (HIF-1α) is overexpressed in cancer, leading to a poor prognosis in patients. Diverse cellular factors are able to regulate HIF-1α expression in hypoxia and even in non-hypoxic conditions, affecting its progression and malignant characteristics by regulating the expression of the HIF-1α target genes that are involved in cell survival, angiogenesis, metabolism, therapeutic resistance, et cetera. Numerous studies have exhibited the anti-cancer effect of HIF-1α inhibition itself and the augmentation of anti-cancer treatment efficacy by interfering with HIF-1α-mediated signaling. The anti-cancer effect of plant-derived phytochemicals has been evaluated, and they have been found to possess significant therapeutic potentials against numerous cancer types. A better understanding of phytochemicals is indispensable for establishing advanced strategies for cancer therapy. This article reviews the anti-cancer effect of phytochemicals in connection with HIF-1α regulation.

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Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases

Cited by 36 publications

References 110 publications

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Identification of Disease-Related 2-Oxoglutarate/Fe (II)-Dependent Oxygenase Based on Reduced Amino Acid Cluster Strategy

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

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