Special Feature: Updated Reviews on Hypoxia
Hypoxia is involved in many pathological and physiological conditions. Since Dr. Gregg L. Semenza first identified HIF-1 alpha in 1991, many researchers have investigated on hypoxia so vigorously, and 14,750 papers have been reported on PubMed by March, 2019. For the convenience of Experimental & Molecular Medicine audience, we present the most updated reviews on the role of hypoxia in diverse human diseases including cancer and aging, and also suggest therapeutic targets in this special issue.
A protein family that plays diverse roles in acute and chronic hypoxia (low oxygen) may prove valuable in developing novel therapies for different diseases. Hypoxia, the short- or long-term depletion of oxygen in cells, tissues and organs, is involved in many disease conditions. Holger Eltzschig at the McGovern Medical School in Houston, USA, and co-workers reviewed research into the roles of a key hypoxia regulator, the hypoxia-inducible factor (HIF) protein group, in diseases affecting the heart, lung, liver and kidneys. HIF protein activity is often beneficial in acute conditions such as myocardial ischemia, sending signals to protect cells and increasing tissue tolerance to hypoxia. However, during chronic hypoxia, HIF signaling may contribute to the progression of disease, for example in pulmonary fibrosis. HIF stabilizers and HIF-induced targets as drugs could prove valuable in future treatments.
Deficient oxygen supplies to the body’s tissues and a reduced ability to deal with the cellular stress of low oxygen availability both contribute to the ageing process. Eui-Ju Yeo from Gachon University in Incheon, South Korea, reviews the links between insufficient oxygen, a condition known as hypoxia, and the functional decline associated with getting old. Yeo highlights the role that the oxygen-sensing proteins known as hypoxia-inducible factors (HIFs) play in facilitating oxygen supply and regulating energy production under limited oxygen conditions. HIFs also interact with a series of signaling proteins that, when abnormally activated, contribute to many aging-associated diseases. Yeo singles out two hypoxia-related health problems, prenatal hypoxia during early brain development and obstructive sleep apnea, and discusses how they can accelerate aging in various ways.
The cancer driver genes IDH1/2, JARID1C/ KDM5C, and UTX/ KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism
Genes involved in the removal of methyl groups from histones associated with DNA can promote or suppress tumor growth depending on the metabolic status of the cancer cell. Hyunsung Park and colleagues at the University of Seoul, South Korea, review current knowledge of two genes encoding histone demethylases which have been identified by The Cancer Genome Atlas (TCGA) project as cancer driver genes. Because these demethylase enzymes rely on cellular metabolites to function, their effect is influenced by metabolic conditions in the tumor microenvironment such as low oxygen. The mechanisms through which changes in histone methylation affect the expression of genes involved in tumor progression remain unknown. Further understanding of how cancer metabolism affects the modification of histones will help guide the development of more effective cancer treatments.