HIF‑1α: Its notable role in the maintenance of oxygen, bone and iron homeostasis (Review)

Abstract

Hypoxia is a characteristic feature of numerous diseases, including metabolic bone disease, solid tumors, cardiovascular diseases, neurodegeneration and inflammation. It is also a risk factor for a poor prognosis in various diseases. Hypoxia-inducible factor-1α (HIF-1α) is activated by hypoxia to regulate a series of pathophysiological pathways, which is of utmost significance for maintaining body homeostasis. The present review highlights the role of the HIF-1α in oxygen, bone and iron homeostasis, and alludes on the biological complexity and dual functions of HIF-1α regulation. In addition, the pathophysiological significance of HIF-1α in bone formation, bone absorption, angiogenesis, erythropoiesis, oxidative stress, energy metabolism, iron death, etc., is discussed An accurate understanding of all these processes may aid in the identification of possible therapeutic targets that may then be used in the treatment of related diseases. However, further studies are required to unravel the extensive complexity of HIF-1α regulation and to develop more precise treatment strategies. Contents1. Introduction 2. Oxygen homeostasis 3. Bone homeostasis 4. Iron homeostasis 5.

Why Is Iron Deficiency/Anemia Linked to Alzheimer’s Disease and Its Comorbidities, and How Is It Prevented?

“…In the cell, this is achieved in two different directions: HIF1α increases the expression of glucose transporters, while the energy sensor AMPK increases glucose import via the Akt2/Glut4 pathway. Both proteins are activated by iron depletion [ 116 , 167 ], thereby causing iron deficiency and, further on, anemia. Supporting these physiological approaches to activate HIF1α by HIF-prolyl hydroxylase inhibitors or AMPK by metformin [ 164 ] might prevent anemia [ 169 ] and protect from mitochondrial dysfunction.…”

“…Under hypoxia, the hydroxylation of the alpha subunits is inhibited, thus stabilizing the HIF1α subunits [ 115 ]. HIF1α, together with HIF1ß, constitutes a transcription factor for several thousand genes and shifts cell metabolism towards oxygen-independent glycolysis [ 116 ]. Two of its target genes code for Glut1 and Glut3.…”

Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective

“…HIF-1 is a crucial regulatory protein that controls oxygen homeostasis and plays a primary role in managing the balance between oxygen supply and demand [24]. Under lowoxygen conditions, the hypoxic environment triggers the synthesis of HIF-1, which then regulates angiogenesis, erythropoiesis, and glycolysis to restore oxygen equilibrium [25]. To comprehend the oxygen requirements necessary to govern the physical environment of a particular tissue, it is imperative to understand oxygen tension in the tendon [26,27].…”

Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality

“…In this study, HIF1A was identified as a key upstream regulator of parathyroid volume and function. HIF, a group of transcription factors, plays a role in the body's response to hypoxia by activating genes that encourage blood vessel growth and anaerobic glycolysis [52]. However, it has been shown that HIF1A expression and the expression of HIF1A-driven genes can be controlled in various ways that do not depend on oxygen [53].…”