Cell and Tissue Hypoxia – The Role of von Hippel-Lindau Gene and Hypoxia Inducible Factor-1
Buněčná a tkáňová hypoxie – úloha von HippelLindau genu a hypoxií indukovaného faktoru-1
Je známo, že hypoxie vede ke zvýšené expresi některých genů s cílem kompenzovat její vliv na organizmusa adaptovat buňky a tkáně na prostředí s nedostatkem kyslíku. Mechanizmus buněčných a tkáňových reakcí nahypoxii byl v posledních letech předmětem intenzivního výzkumu. Nejdéle známou komponentou tohoto mechanizmuje hypoxií indukovaný faktor-1 (HIF-1), jehož množství při hypoxii v buňce stoupá. Navázáním na regulačníoblasti citlivých genů zvyšuje jejich transkripci. Zcela nedávno byly popsány jeho další klíčové části – von HippelůvLindaův protein a prolylhydroxylázy, které při dostatečném množství kyslíku umožňují degradaci α-podjednotkyHIF-1. Tím je v buňkách s fyziologickou koncentrací kyslíku udržována nízká hladina HIF-1 a transkripce cílovýchgenu probíhá na bazální úrovni. Tyto nové poznatky jsou východiskem dalšího poznání a případného terapeutickéhovyužití.
Klíčová slova:
hypoxie, von Hippel Lindau, hypoxií indukovaný faktor-1, regulace genové exprese.
Authors:
V. Sýkora; E. Nečas
Authors‘ workplace:
Ústav patologické fyziologie 1. LF UK, Praha
Published in:
Čas. Lék. čes. 2003; : 595-598
Category:
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.
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