Cell and Tissue Hypoxia – The Role of von Hippel-Lindau Gene and Hypoxia Inducible Factor-1

Overview

Hypoxia results in increased expression of some genes. This can compensate effects of hypoxia on the organism,and adapt cells and tissues to the environment with low oxygen tension. Mechanisms of cell and tissue responses tohypoxia have been extensively studied last years. The first identified mediator of cell response to hypoxia washypoxia-inducible factor (HIF-1), which is being up regulated during hypoxic conditions. It binds to regulatoryregions of sensitive genes and increases their transcription rate. Other key elements of cell response to hypoxia havebeen described recently – von Hippel-Lindau protein and prolyl hydroxylases, that allow degradation of α-subunitof HIF-1 during normal oxygen tension. This can ensure low level of HIF-1 in cells under physiological oxygentension thus the expression of target genes is maintained on basal level. These new findings are starting points forfurther research and possible therapeutic use.

Key words:
hypoxia, von Hippel-Lindau, hypoxia inducible factor-1, regulation of gene expression.