Histone Deacetylase Inhibition Attenuates Transcriptional Activity of Mineralocorticoid Receptor Through Its Acetylation and Prevents Development of Hypertension

Lee, Hae-Ahm; Lee, Dong-Youb; Cho, Hyunmin; Kim, Sangjin; Iwasaki, Yoshinobu; Kim, In Kyeom

doi:10.1161/circresaha.113.301071

Cited by 99 publications

(112 citation statements)

References 39 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…3). Acetylation of lysine in the hinge region of MR resulted in transcriptional repression of MR (Lee et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…However, post-transcriptional modifications, such as acetylation, phosphorylation, ubiquitylation, and sumoylation, play critical roles in regulating its transcriptional activity (Faus and Haendler, 2006). Phosphorylation of MR enhances its binding affinity for DNA response elements (Massaad et al, 1999), whereas acetylation of MR inhibits recruitment of MR and RNA polymerase II (Pol II) on promoter of MR target genes and prevents development of hypertension (Lee et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Histone Deacetylase Inhibition Attenuates Cardiac Hypertrophy and Fibrosis through Acetylation of Mineralocorticoid Receptor in Spontaneously Hypertensive Rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

Inhibition of histone deacetylases (HDACs) by valproic acid (VPA) attenuates inflammatory, hypertrophic, and fibrotic responses in the hearts of spontaneously hypertensive rats (SHRs); however, the molecular mechanism is still unclear. We hypothesized that HDAC inhibition (HDACi) attenuates cardiac hypertrophy and fibrosis through acetylation of mineralocorticoid receptor (MR) in SHRs. Seven-week-old SHRs and Wistar-Kyoto rats were treated with an HDAC class I inhibitor (0.71% w/v in drinking water; VPA) for 11 weeks. Sections of heart were visualized after trichrome stain as well as H&E stain. Histone modifications, such as acetylation (H3Ac [acetylated histone 3]) and fourth lysine trimethylation (H3K4me3) of histone 3, and recruitment of MR and RNA polymerase II (Pol II) into promoters of target genes were measured by quantitative real-time polymerase chain reaction after chromatin immunoprecipitation assay. MR acetylation was determined by Western blot with anti-acetyl-lysine antibody after immunoprecipitation with anti-MR antibody. Treatment with VPA attenuated cardiac hypertrophy and fibrosis. Although treatment with VPA increased H3Ac and H3K4me3 on promoter regions of MR target genes, expression of MR target genes as well as recruitment of MR and Pol II on promoters of target genes were decreased. Although HDACi did not affect MR expression, it increased MR acetylation. These results indicate that HDACi attenuates cardiac hypertrophy and fibrosis through acetylation of MR in spontaneously hypertensive rats.

show abstract

“…3). Acetylation of lysine in the hinge region of MR resulted in transcriptional repression of MR (Lee et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Histone Deacetylase Inhibition Attenuates Cardiac Hypertrophy and Fibrosis through Acetylation of Mineralocorticoid Receptor in Spontaneously Hypertensive Rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Welsbie et al (39) determined that KDACs 1 and 3 were largely responsible for promoting androgen receptor transactivation in LNCaP cells, whereas KDAC3 has been shown to potentiate mineralocorticoid receptor transactivation in HEK293 cells (40). Several studies suggest a positive relationship between KDAC activity and promoter association of RNA polymerase (pol) II.…”

Section: Discussionmentioning

confidence: 99%

Class I Lysine Deacetylases Facilitate Glucocorticoid-induced Transcription

Kadiyala¹,

Patrick²,

Mathieu³

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…A consensus glucocorticoid response element (GRE) is located at position K429/K414 in the human serum-and glucocorticoid-regulated kinase 1 (Sgk1) promoter; chromatin immunoprecipitation (ChiP) data have shown that MR directly binds this region of the Sgk1 gene and stimulates its transcription in embryonic kidney 293 cells (HEK293) (Lee et al 2013). SGK1 has been shown to mediate aldosteroneinduced NaC reabsorption by renal epithelia (McCormick et al 2005), but a role for Sgk1 has been also demonstrated in adipocyte differentiation (Di Pietro et al 2010).…”

Section: Role Of Mr In Regulating Adipogenesis-linked Signaling Pathwaysmentioning

confidence: 99%

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

Armani¹,

Marzolla²,

Fabbri³

et al. 2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity.

show abstract

Histone Deacetylase Inhibition Attenuates Transcriptional Activity of Mineralocorticoid Receptor Through Its Acetylation and Prevents Development of Hypertension

Cited by 99 publications

References 39 publications

Histone Deacetylase Inhibition Attenuates Cardiac Hypertrophy and Fibrosis through Acetylation of Mineralocorticoid Receptor in Spontaneously Hypertensive Rats

Histone Deacetylase Inhibition Attenuates Cardiac Hypertrophy and Fibrosis through Acetylation of Mineralocorticoid Receptor in Spontaneously Hypertensive Rats

Class I Lysine Deacetylases Facilitate Glucocorticoid-induced Transcription

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

Contact Info

Product

Resources

About