HIF-1: a key mediator in hypoxia (Review)

The transcription factor HIF-1 is one of the principal mediators of homeostasis in human tissues exposed to hypoxia. It is implicated in virtually every process of rapid gene expression in response to low oxygen levels. The most common causes of tissue hypoxia are inflammation and/or insufficient circulation or a combination of both. Inflamed tissues and the areas surrounding malignant tumors are characterized by hypoxia and low concentrations of glucose. Serious and generalized inflammation can lead to sepsis and circulatory collapse resulting in acute or chronic tissue hypoxia in various vital organs which induces a rapid homeostatic process in all nucleated cells of affected organs in the human body. Under hypoxic conditions the alpha and beta subunits of HIF-1 make an active heterodimer and drive the transcription of over 60 genes important for cell survival, adaptation, anaerobic metabolism, immune reaction, cytokine production, vascularization and general tissue homeostasis. In addition, HIF-1 plays a key role in the development of physiological systems in fetal and postnatal life. It is also a critical mediator of cancer, lung and cardiovascular diseases. The better understanding of the functions of HIF-1 and the pharmacological modulation of its activity could mean a successful therapeutic approach to these diseases

The biology of A20-binding inhibitors of NF-κB activation (ABINs)

The family of A20‑Binding Inhibitors of NF‑kB (ABINs) consists of three proteins, ABIN‑1, ABIN‑2 and ABIN‑3, which were originally identified as A20‑binding proteins and inhibitors of cytokines and Lipopolysaccharide (LPS) induced NF‑kB activation. ABIN family members have limited sequence homology in a number of short regions that mediate A20‑binding, ubiquitin‑binding, and NF‑kB inhibition. The functional role of A20 binding to ABINs remains unclear, although an adaptor function has been suggested. ABIN‑1 and ABIN‑3 expression is upregulated when cells are triggered by NF‑kB‑activating stimuli, suggesting a role for these ABINs in a negative feedback regulation of NF‑kB signaling. Additional ABIN functions have been reported such as inhibition of TNF‑induced hepatocyte apoptosis, regulation of HIV‑1 replication for ABIN‑1, and Tumor Progression Locus 2 (TPL‑2)‑mediated Extracellular signal‑Regulated Kinase (ERK) activation for ABIN‑2. In mice, ABIN‑1 overexpression reduces allergic airway inflammation and TNF‑mediated liver injury, ABIN‑2 overexpression delays liver regeneration, and ABIN‑3 overexpression partially protects against LPS‑induced acute liver failure. Analysis of mice deficient in ABIN‑1 or ABIN‑2 demonstrates the important immune regulatory function of ABINs. Future studies should clarify the functional implication of the A20‑ABIN interaction in supporting ABINs’ mechanisms of action

A Surface Scientist's view on Spectroscopic Ellipsometry

none1noneMaurizio CanepaCanepa, Maurizi