Synergistic effects of hypoxia and insulin are regulated by different transcriptional elements of the human leptin promoter.
Biochem Biophys Res Commun
; 303(2): 707-12, 2003 Apr 04.
Article
in En
| MEDLINE
| ID: mdl-12659876
ABSTRACT
Leptin is a regulator on placenta and conceptus during pregnancy. Hyperinsulinism and hypoxia induce partially overlapping pathophysiological disturbances during pregnancy. As insulin and hypoxia are known inducers of leptin secretion, we asked whether these two stimuli have synergistic effects. By analyzing mRNA levels of leptin after stimulation of BeWo cells with insulin in the presence or absence of oxygen, we found a supraadditive effect when incubating hypoxic cells with insulin. As shown by Western-blot of hypoxia-inducible-factor-1 alpha (HIF-1 alpha), the additive effects of these stimuli were not mediated by an increased stabilization of the HIF-complex. We therefore asked what elements of the leptin promoter are responsible for these effects. When deleting a 0.6 kb fragment of the cloned leptin promoter, a so far unknown loss of insulin-dependent activation of transcription, as well as a loss of the supraadditive effect of insulin and hypoxia could be observed. These results provide strong evidence that insulin and hypoxia act as agonists on the human leptin transcription but on two different regulatory elements.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Cell Hypoxia
/
Gene Expression Regulation
/
Promoter Regions, Genetic
/
Leptin
/
Insulin
Limits:
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2003
Document type:
Article
Affiliation country: