Regulation of glycolysis by the hypoxia‐inducible factor (HIF): implications for cellular physiology

The Journal of Physiology, Journal Year: 2020, Volume and Issue: 599(1), P. 23 - 37

Published: Oct. 2, 2020

Under conditions of hypoxia, most eukaryotic cells can shift their primary metabolic strategy from predominantly mitochondrial respiration towards increased glycolysis to maintain ATP levels. This hypoxia-induced reprogramming metabolism is key satisfying cellular energetic requirements during acute hypoxic stress. At a transcriptional level, this switch be regulated by several pathways including the hypoxia inducible factor-1α (HIF-1α) which induces an expression glycolytic enzymes. While increase in flux beneficial for maintaining bioenergetic homeostasis mediating also exploited cancer promote tumour survival and growth, area has been extensively studied. It recently become appreciated that may have profound effects on physiology immune endothelial cells. Therefore, understanding mechanisms central are importance both physiological pathophysiological standpoints. In review, we highlight role HIF-1α regulation its implications processes such as angiogenesis cell effector function.

Language: Английский

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The role of microenvironment in tumor angiogenesis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Sept. 30, 2020

Abstract Tumor angiogenesis is necessary for the continued survival and development of tumor cells, plays an important role in their growth, invasion, metastasis. The microenvironment—composed surrounding secreted cytokines—provides a conducive environment growth tumors. Different components microenvironment can regulate development. In this review, we have discussed regulatory angiogenesis. High expression angiogenic factors inflammatory cytokines microenvironment, as well hypoxia, are presumed to be reasons poor therapeutic efficacy current anti-angiogenic drugs. A combination drugs antitumor or hypoxia inhibitors might improve outcome.

Language: Английский

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The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 66, P. 101249 - 101249

Published: Dec. 29, 2020

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism response to changes in the inflammatory microenvironment may play key role cartilage degeneration OA progression. Under conditions environmental stress, chondrocytes tend adapt their microenvironmental shifting from one metabolic pathway another, for example oxidative phosphorylation glycolysis. Similar occur other cells, including synoviocytes. Switching between these pathways implicated alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, altered lipid amino acid metabolism. The shift glycolysis mainly regulated AMP-activated protein kinase (AMPK) mechanistic target rapamycin (mTOR) pathways. Chondrocyte are likely be feature different phenotypes. Determining has revealed features pathogenesis. Future research should place greater emphasis on immunometabolism as means understand pathophysiology age-related OA. This knowledge will advance development new drugs against therapeutic targets significance.

Language: Английский

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Conquering the Hypoxia Limitation for Photodynamic Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(48)

Published: Sept. 27, 2021

Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due the hypoxic nature characteristic of many solid tumors, PDT is frequently limited therapeutic effect. Moreover, consumption O2 during may further aggravate tumor condition, which promotes proliferation, metastasis, invasion resulting poor prognosis treatment. Therefore, numerous efforts have been made increase content with goal enhancing efficacy. Herein, these strategies developed past decade are comprehensively reviewed alleviate hypoxia, including 1) delivering exogenous directly, 2) generating situ, 3) reducing cellular by inhibiting respiration, 4) regulating TME, (e.g., normalizing vasculature or disrupting extracellular matrix), 5) hypoxia-inducible factor 1 (HIF-1) signaling pathway relieve hypoxia. Additionally, -independent Type-I also discussed as an alternative strategy. By reviewing progress, it hoped that this review will provide innovative perspectives new nanomaterials designed combat hypoxia avoid associated limitation PDT.

Language: Английский

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The double-edged roles of ROS in cancer prevention and therapy

Theranostics, Journal Year: 2021, Volume and Issue: 11(10), P. 4839 - 4857

Published: Jan. 1, 2021

Reactive oxygen species (ROS) serve as cell signaling molecules generated in oxidative metabolism and are associated with a number of human diseases. The reprogramming redox induces abnormal accumulation ROS cancer cells. It has been widely accepted that play opposite roles tumor growth, metastasis apoptosis according to their different distributions, concentrations durations specific subcellular structures. These double-edged progression include the ROS-dependent malignant transformation stress-induced death. In this review, we summarize notable literatures on generation scavenging, discuss related signal transduction networks corresponding anticancer therapies. There is no doubt an improved understanding sophisticated mechanism biology imperative conquer cancer.

Language: Английский

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Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126

Acta Biomaterialia, Journal Year: 2019, Volume and Issue: 103, P. 196 - 212

Published: Dec. 17, 2019

Language: Английский

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HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(10), P. 5074 - 5087

Published: Sept. 1, 2020

Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis metabolic rewiring are well-established drivers of breast aggressiveness, therapy resistance, poor prognosis. Targeting HIF its downstream targets in metabolism has been unsuccessful so far clinical setting, with major unresolved challenges residing target selection, development robust biomarkers for response prediction, understanding harnessing escape mechanisms. This Review discusses pathophysiological role HIFs, angiogenesis, targeting these features patients cancer. Rational therapeutic combinations, especially immunotherapy endocrine therapy, seem most promising exploitation intricate interplay cells tumor microenvironment.

Language: Английский

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Hypoxia and hypoxia-inducible factors in diabetes and its complications

Diabetologia, Journal Year: 2021, Volume and Issue: 64(4), P. 709 - 716

Published: Jan. 26, 2021

Abstract Hypoxia-inducible factors (HIFs) are the key regulators of oxygen homeostasis in response to hypoxia. In diabetes, multiple tissues hypoxic but adaptive responses hypoxia impaired due insufficient activation HIF signalling, which results from inhibition HIF-1α stability and function hyperglycaemia elevated fatty acid levels. this review, we will summarise discuss current findings about regulation signalling diabetes pathogenic roles dysregulated development its complications. The therapeutic potential targeting for prevention treatment related complications is also discussed. Graphical abstract

Language: Английский

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Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine

Journal of Biological Chemistry, Journal Year: 2020, Volume and Issue: 295(30), P. 10493 - 10505

Published: June 6, 2020

The gastrointestinal tract is a highly proliferative and regenerative tissue. intestine also harbors large diverse microbial population collectively called the gut microbiome (microbiota). microbiome-intestine cross-talk includes dynamic exchange of gaseous signaling mediators generated by bacterial intestinal metabolisms. Moreover, initiates maintains hypoxic environment that critical for nutrient absorption, barrier function, innate adaptive immune responses in mucosal cells intestine. response to hypoxia mediated hypoxia-inducible factors (HIFs). In conditions, HIF activation regulates expression cohort genes promote adaptation hypoxia. Physiologically, HIF-dependent contribute aforementioned maintenance epithelial regulation. However, chronic exacerbates disease leading injury, inflammation, colorectal cancer. this review, we aim outline major roles physiological pathological conditions homeostasis onset progression with focus on understanding complex pathophysiology

Language: Английский

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Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 7, 2022

Abstract Molecular oxygen (O 2 ) is essential for most biological reactions in mammalian cells. When the intracellular content decreases, it called hypoxia. The process of hypoxia linked to several processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, other stress responses. mechanism underlying cells respond changes mediate subsequent signal response central question during Hypoxia-inducible factors (HIFs) sense regulate expressions a series downstream genes expression, which participate multiple processes cell metabolism, growth/death, proliferation, glycolysis, immune response, tumorigenesis, metastasis. Importantly, signaling also interacts with cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) endoplasmic reticulum (ER) stress. This paper systematically reviews mechanisms activation, control HIF function human health diseases. In addition, therapeutic targets involved balance diseases are summarized highlighted, would provide novel strategies design development drugs.

Language: Английский

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