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The Role of HIF-1a in Animal Physiology and Biochemistry
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The Role of HIF-1a in Animal Physiology and Biochemistry

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 16986

Special Issue Editors

Prof. Dr. Zhengchao Wang

E-Mail Website
Guest Editor
College of Life Sciences, Fujian Normal University, Fuzhou 350007, Fujian, China
Interests: hypoxia inducible factor-1a; follicular development; luteal formation and degeneration; transcriptome and proteome; polycystic ovary syndrome
Prof. Dr. Ningjun Li

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
Interests: hypertension; renal injury; pharmacology; chemonephrotoxicity; molecular mechanisms of chronic kidney failure
Special Issues, Collections and Topics in MDPI journals
Dr. Yang Zhang

E-Mail Website
Guest Editor
Department of Pharmacological & Pharmaceutic, University of Houston, Houston, TX 77204, USA
Interests: hypoxia inducible factor-1a; microvascular injury; arterial smooth muscle cells; Nlrp3 inflammasome; lysosome biogenesis and function; hyperlipidemia and atherosclerosis

Special Issue Information

Dear Colleagues,

Hypoxia inducible factor (HIF) is an important factor in allowing the body to perceive oxygen, which was first discovered by Professor Semenza in 1995, who won the Nobel Prize in physiology and medicine in 2019. The oxygen produced in the earth's atmospheric environment is an important factor for the occurrence and development of all organisms. The respiratory and circulatory system of organisms can effectively obtain oxygen and use oxygen to achieve its purpose of survival. Under hypoxia, HIF-1a hydroxylation is inhibited and then bound with HIF-1b subunits to form HIF-1a/b heterodimers, which enter the nucleus and bind with the hypoxia responsive element (HRE) to activate the transcription of target genes. Our previous studies also found that HIF-1a is not only regulated by hypoxic microenvironments, but also by many chemical molecules in vivo, such as hormones and cytokines. Given the role of biological macromolecule HIF-1a in physiopathological processes, many specific small molecule compounds and natural products targeting HIF-1a are attracting more and more attention, accompanied by the development of nanomaterials and chemical modification for the chemical delivery of such substances. To increase the specificity of these drugs and their bioavailabilities, several feasible approaches and some pharmaceutical investigations can be undertaken with special interest, both in academia and in the pharmaceutical industry. These include HIF-1a-specific small molecule inhibitors (such as echinomycin and oltipraz), drug delivery systems based on lipids and nanomaterials, and the molecules that interact with HIF-1a in vivo. This Special Issue aims to provide a forum to disseminate the latest information on the specificity, bioavailability, and delivery of these chemical drugs and natural products—and their pharmaceutical effects during disease processes.

Prof. Dr. Zhengchao Wang
Prof. Dr. Ningjun Li
Dr. Yang Zhang
Guest Editors

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Keywords

  • hypoxia inducible factor-1a
  • chronic kidney diseases
  • salt-sensitive hypertension
  • chronic ischemic renal injury
  • hyperlipidemia and atherosclerosis
  • polycystic ovary syndrome
  • luteal formation and degeneration

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Published Papers (3 papers)

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Research

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14 pages, 2645 KiB  
Article
Paclitaxel Induces the Apoptosis of Prostate Cancer Cells via ROS-Mediated HIF-1α Expression
by Yan Zhang, Yedong Tang, Xiaoqiong Tang, Yuhua Wang, Zhenghong Zhang and Hongqin Yang
Molecules 2022, 27(21), 7183; https://doi.org/10.3390/molecules27217183 - 24 Oct 2022
Cited by 13 | Viewed by 3185
Abstract
Prostate cancer (PCa) is the most common malignancy to endanger the health of male genitourinary system. Clinically, paclitaxel (PTX) (C47H51NO14), a diterpene alkaloid, is commonly used as an effective natural antineoplastic drug during the treatment of PCa. However, the mechanism and pathway involved [...] Read more.
Prostate cancer (PCa) is the most common malignancy to endanger the health of male genitourinary system. Clinically, paclitaxel (PTX) (C47H51NO14), a diterpene alkaloid, is commonly used as an effective natural antineoplastic drug during the treatment of PCa. However, the mechanism and pathway involved in the function of PTX are poorly understood. In the current study, we employed the CCK-8 assay, revealing that PTX can inhibit the survival and induce the apoptosis of PC3M cells (a human prostate cancer cell line) in a concentration-dependent manner. Reactive oxygen species (ROS), as a metabolic intermediate produced by the mitochondrial respiratory chain, are highly accumulated under the PTX treatment, which results in a sharp decrease of the mitochondrial membrane potential in PC3M cells. Additionally, the migration and invasion of PC3M cells are weakened due to PTX treatment. Further analysis reveals that N-acetylcysteine (NAC), which functions as an antioxidant, not only rescues the decreased mitochondrial membrane potential induced by the abnormal ROS level, but also restores the migration and invasion of PC3M cells. In a subsequent exploration of the detailed mechanism, we found that hypoxia-inducible factor (HIF)-1α works as a downstream gene that can respond to the increased ROS in PC3M cells. Under PTX treatment, the expression levels of HIF-1α mRNA and protein are significantly increased, which stimulate the activation of JNK/caspase-3 signaling and promote the apoptosis of PC3M cells. In summary, we demonstrate that PTX regulates the expression of HIF-1α through increased ROS accumulation, thereby promoting the activation of JNK/caspase-3 pathway to induce the apoptosis of PCa cells. This study provides new insights into the mechanism of antineoplastic action of taxanes and unveils the clinical benefit of the ROS-HIF-1α signaling pathway, which may offer a potential therapeutic target to prevent the development of PCa. Full article
(This article belongs to the Special Issue The Role of HIF-1a in Animal Physiology and Biochemistry)
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Review

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13 pages, 1846 KiB  
Review
The Role of Hypoxia-Inducible Factor-1 Alpha in Renal Disease
by Huixia Liu, Yujuan Li and Jing Xiong
Molecules 2022, 27(21), 7318; https://doi.org/10.3390/molecules27217318 - 28 Oct 2022
Cited by 17 | Viewed by 6722
Abstract
Partial pressure of oxygen (pO2) in the kidney is maintained at a relatively stable level by a unique and complex functional interplay between renal blood flow, glomerular filtration rate (GFR), oxygen consumption, and arteriovenous oxygen shunting. The vulnerability of this interaction [...] Read more.
Partial pressure of oxygen (pO2) in the kidney is maintained at a relatively stable level by a unique and complex functional interplay between renal blood flow, glomerular filtration rate (GFR), oxygen consumption, and arteriovenous oxygen shunting. The vulnerability of this interaction renders the kidney vulnerable to hypoxic injury, leading to different renal diseases. Hypoxia has long been recognized as an important factor in the pathogenesis of acute kidney injury (AKI), especially renal ischemia/reperfusion injury. Accumulating evidence suggests that hypoxia also plays an important role in the pathogenesis and progression of chronic kidney disease (CKD) and CKD-related complications, such as anemia, cardiovascular events, and sarcopenia. In addition, renal cancer is linked to the deregulation of hypoxia pathways. Renal cancer utilizes various molecular pathways to respond and adapt to changes in renal oxygenation. Particularly, hypoxia-inducible factor (HIF) (including HIF-1, 2, 3) has been shown to be activated in renal disease and plays a major role in the protective response to hypoxia. HIF-1 is a heterodimer that is composed of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit. In renal diseases, the critical characteristic of HIF-1α is protective, but it also has a negative effect, such as in sarcopenia. This review summarizes the mechanisms of HIF-1α regulation in renal disease. Full article
(This article belongs to the Special Issue The Role of HIF-1a in Animal Physiology and Biochemistry)
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14 pages, 1225 KiB  
Review
Action Sites and Clinical Application of HIF-1α Inhibitors
by Renfeng Xu, Fan Wang, Hongqin Yang and Zhengchao Wang
Molecules 2022, 27(11), 3426; https://doi.org/10.3390/molecules27113426 - 26 May 2022
Cited by 25 | Viewed by 6573
Abstract
Hypoxia-inducible factor-1α (HIF-1α) is widely distributed in human cells, and it can form different signaling pathways with various upstream and downstream proteins, mediate hypoxia signals, regulate cells to produce a series of compensatory responses to hypoxia, and play an important role in the [...] Read more.
Hypoxia-inducible factor-1α (HIF-1α) is widely distributed in human cells, and it can form different signaling pathways with various upstream and downstream proteins, mediate hypoxia signals, regulate cells to produce a series of compensatory responses to hypoxia, and play an important role in the physiological and pathological processes of the body, so it is a focus of biomedical research. In recent years, various types of HIF-1α inhibitors have been designed and synthesized and are expected to become a new class of drugs for the treatment of diseases such as tumors, leukemia, diabetes, and ischemic diseases. This article mainly reviews the structure and functional regulation of HIF-1α, the modes of action of HIF-1α inhibitors, and the application of HIF-1α inhibitors during the treatment of diseases. Full article
(This article belongs to the Special Issue The Role of HIF-1a in Animal Physiology and Biochemistry)
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