Oxygen Sensing and Molecular Adaptation to Hypoxia.
Bunn, H. Franklin, and Robert O. Poyton.
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusettes; and Department of Molecular, Cellular,
and Developmental Biology, University of Colorado at Boulder, Boulder,
Colorado.
APStracts 2:0015P, 1996.
ABSTRACT
This review focuses on the molecular stratagems utilized by bacteria, yeast,
and mammals in their adaptation to hypoxia. Among this broad range of
organisms, changes in oxygen tension appear to be sensed by heme proteins,
with subsequent transfer of electrons along a signal transduction pathway
which may depend upon reactive oxygen species. These heme-based sensors are
generally two-domain proteins. Some are hemokinases, while others are
flavohemoproteins [ob]flavohemoglobins and NAD(P)H oxidases[cb]. Hypoxia-
dependent kinase activation of transcription factors in nitrogen-fixing
bacteria bears a striking analogy to the phosphorylation of hypoxia inducible
factor-1 (HIF-1) in mammalian cells. Moreover, redox chemistry appears to play
a critical role both in the [i]trans[r]-activation of oxygen-responsive genes
in unicellular organisms as well as in the activation of HIF-1. In yeast and
bacteria, regulatory operons coordinate expression of genes responsible for
adaptive responses to hypoxia and hyperoxia. Similarly, in mammals,
combinatorial interactions of HIF-1 with other identified transcription
factors are required for the hypoxic induction of physiologically important
genes.
APS Manuscript Number P-6.
Article publication pending July 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96