The ability to maintain O(2) homeostasis is essential to the survival of all invertebrate and vertebrate species. The transcriptional factor, hypoxia inducible factor 1 (HIF-1), is the principal regulator of oxygen homeostasis. Under hypoxic condition HIF-1 induces the transcription of several hypoxia-responsive genes by binding to hypoxia-response elements (HRE) in their promoters. In recent years it has been demonstrated that hypoxia could be related to metabolic variations such as hyper-cholesterolemia in mouse models. On the basis of this observation, the present study was performed to verify the involvement of HIF-1, and in particular the effect of chemical and environmental induction of HIF-1alpha (the oxygen sensitive isoform) accumulation in 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR, the key and rate limiting enzyme of cholesterol biosynthetic pathway) regulation. Our results show that HIF-1alpha accumulation is able to increase level and activity of HMG-CoAR by stimulating its transcription. The raised transcription of the reductase could be related to an induction by HIF-1alpha even if a parallel action of SREBP-2 actively translocated to nucleus by the increased level of SCAP cannot be excluded.
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|Titolo:||Regulation of HMG-CoA reductase expression by hypoxia.|
|Rivista:||JOURNAL OF CELLULAR BIOCHEMISTRY|
|Citazione:||Pallottini, V., Guantario, B., Martini, C., Totta, P., Filippi, I., Carraro, F., et al. (2008). Regulation of HMG-CoA reductase expression by hypoxia. JOURNAL OF CELLULAR BIOCHEMISTRY, 104(3), 701-709.|
|Appare nelle tipologie:||1.1 Articolo in rivista|