Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5. FASEB J 2006 Oct;20(12):2127-9
Date
08/31/2006Pubmed ID
16940436DOI
10.1096/fj.06-6179fjeScopus ID
2-s2.0-33845662610 (requires institutional sign-in at Scopus site) 68 CitationsAbstract
Uteroplacental insufficiency leads to intrauterine growth retardation (IUGR) and adult onset insulin resistance in both humans and rats. IUGR rat liver is characterized by persistent changes in histone 3 lysine 9 and lysine 14 acetylation, which may induce postnatal changes in gene expression. We hypothesized that it would be possible to identify hepatic genes whose epigenetic characteristics and mRNA levels are altered due to IUGR using chromatin immunoprecipitation (ChIP) coupled with random primed differential display polymerase chain reaction (PCR). One of the isolated sequences identified contained exon 2 of the dual specificity phosphatase-5 gene (DUSP5). IUGR affected hepatic DUSP5 mRNA levels and exon 2 DNA methylation into adulthood in the rat. DUSP5 dephosphorylates Erk1 and Erk2 within the MAPK signaling cascade, which in turn affects serine 612 phosphorylation of insulin receptor substrate-1 (p612 IRS-1). In adult rat liver, IUGR increased Erk1/Erk2 phosphorylation and p612 IRS-1 phosphorylation. Increased serine phosphorylation of hepatic IRS-1 may contribute to the insulin resistance that characterizes these animals. We conclude that intrauterine growth retardation induced by uteroplacental insufficiency 1) affects the hepatic epigenetic characteristics and mRNA of the DUSP-5 and 2) increases hepatic insulin receptor substrate-1 phosphorylation at serine 612 in adult rats.
Author List
Fu Q, McKnight RA, Yu X, Callaway CW, Lane RHMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
DNA Methylation
Dual-Specificity Phosphatases
Epigenesis, Genetic
Female
Fetal Growth Retardation
Insulin Receptor Substrate Proteins
Liver
MAP Kinase Signaling System
Male
Models, Animal
Phosphoproteins
Phosphorylation
Pregnancy
Protein Tyrosine Phosphatases
RNA, Messenger
Rats
