Hepatocyte nuclear factor-4α, a multifunctional nuclear receptor associated with cardiovascular disease and cholesterol catabolism.
Cardiovascular diseases (CVDs), the leading cause of death worldwide, are associated with high plasma cholesterol levels. The conversion of cholesterol to bile acids (BAs) accounts for about 50% of total cholesterol elimination from the body. This phenomenon occurs in the liver and is regulated by nuclear receptors such as hepatocyte nuclear factor-4α (HNF-4α). Therefore, special emphasis is given to HNF-4α properties and its multifunctional role, particularly in the conversion of cholesterol to BAs. HNF-4α is a highly conserved transcription factor that has the potential capacity to transactivate a vast number of genes, including CYP7 which codes for cholesterol 7α-hydroxylase (CYP7A1; EC 1.14.13.17), the rate-limiting enzyme of BA biosynthesis. The fact that HNF-4α transactivation potential can be modulated via phosporylation is of particular interest. Additional findings on structural and functional characteristics of HNF-4α may eventually present alternatives to control the levels of cholesterol in the body and consequently reduce the risk of CVDs.
a Departamento de Biotecnología y Ciencias Alimentarias , Instituto Tecnológico de Sonora , Ciudad Obregón , Mexico.
Olga Lidia
OL
Tavares-Sanchez
Carmen
C
Rodriguez
Pablo
P
Gortares-Moroyoqui
Maria Isabel
MI
Estrada
D000595:Amino Acid Sequence; D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D051381:Rats; D016415:Sequence Alignment
C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; C496594:Hnf4a protein, rat; D002784:Cholesterol
HNF-4α; cardiovascular disease; cholesterol; nuclear receptor; phosphorylation