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Hypoxia-inducible transcription factor-1 (HIF-1) is a master regulator of hypoxia-induced gene responses. To find out whether HIF-1 function is involved in gene expression changes associated with temperature acclimation as well as in hypoxia adaptation in poikilotherms, we studied HIF-1 DNA binding activity and HIF-1alpha expression in normoxia and during hypoxia (0.7 mg l(-1) O2) in crucian carp at temperatures of 26, 18 and 8 degrees C. Temperature had a marked influence on HIF-1 in normoxia. Although HIF-1alpha mRNA levels remained unaltered, cold acclimation (8 degrees C) increased HIF-1alpha protein amounts in the liver, gills and heart and HIF-1 DNA binding activity in the heart, gills and kidney of crucian carp by two- to threefold compared to warm acclimated fish (26 degrees C). In the heart and kidney HIF-1 activity was already significantly increased in the 18 degrees C acclimated fish. Temperature also affected hypoxic regulation of HIF-1. Although hypoxia initially increased amounts of HIF-1alpha protein in all studied tissues at every temperature, except for liver at 18 degrees C, HIF-1 activity increased only in the heart of 8 degrees C acclimated and in the gills of 18 degrees C acclimated fish. At 8 degrees C HIF-1alpha mRNA levels increased transiently in the gills after 6 h of hypoxia and in the kidney after 48 h of hypoxia. In the gills at 26 degrees C HIF-1alpha mRNA levels increased after 6 h of hypoxia and remained above normoxic levels for up to 48 h of hypoxia. These results show that HIF-1 is involved in controlling gene responses to both oxygen and temperature in crucian carp. No overall transcriptional control mechanism has been described for low temperature acclimation in poikilotherms, but the present results suggest that HIF-1 could have a role in such regulation. Moreover, this study highlights interaction of the two prime factors defining metabolism, temperature and oxygen, in the transcriptional control of metabolic homeostasis in animals.
Rissanen et al. (Thu,) studied this question.