Chronic in vivo hypoxia in various organs: hypoxia-inducible factor-1alpha and apoptosis.
We studied the in vivo persistence of hypoxia-inducible factor-1alpha (HIF-1alpha), main transducer of hypoxia, the differential response in organs exposed to the same degree of hypoxemia and the relationship with apoptosis. We measured HIF-1alpha (immunohistochemistry peroxidase and Western blot) and apoptosis (TUNEL) in heart, liver, kidney, gastrocnemius, and brain of rats exposed to chronic normobaric hypoxia (10% O2) or normoxia (21% O2) for 2 weeks. Despite same arterial O2 pressure and increased hemoglobin concentration (219 +/- 5 vs. 124 +/- 4 g/L), the organs responded differently. While marked in brain, muscle, and kidney cortex, HIF-1alpha was undetectable in heart and liver. In kidney medulla, HIF-1alpha was high in both normoxia and hypoxia. By contrast, apoptosis was marked in heart, slight in kidney medulla, and undetectable in other organs. We conclude that the HIF-1alpha response to chronic hypoxia can be a sustained phenomenon, but not in all organs, and that apoptosis responds differently from HIF-1alpha.
Bianciardi
Paola
P
Department of Medicine, Surgery, and Dentistry, University of Milan, San Paolo Hospital, Milan, Italy.
Fantacci
Monica
M
Caretti
Anna
A
Ronchi
Raffaella
R
Milano
Giuseppina
G
Morel
Sandrine
S
von Segesser
Ludwig
L
Corno
Antonio
A
Samaja
Michele
M
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
D051795:Hypoxia-Inducible Factor 1, alpha Subunit