DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development

Ghosh, Krishna; Zhou, Jing-Jing; Shao, Jian-Ying; Chen, Shao-Rui; Pan, Hui-Lin

doi:10.1016/j.jbc.2023.105597

Cited by 2 publications

(2 citation statements)

References 73 publications

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“…DNA methylation is an essential epigenetic mechanism that regulates gene expression. Decreased DNA methylation in gene promoters usually leads to the activation of gene transcription, while increased methylation often inhibits gene expression [50]. Phosphorylation has emerged as a key means to rapidly and reversibly modulate the intrinsic transport activity of NKCC1 and KCC2 as a potential therapeutic effect by regulating [Cl − ]i levels [51,52].…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylation has emerged as a key means to rapidly and reversibly modulate the intrinsic transport activity of NKCC1 and KCC2 as a potential therapeutic effect by regulating [Cl − ]i levels [51,52]. The activity of NKCC1 is precisely regulated by protein phosphorylation and dephosphorylation, where several kinases have been proposed to regulate NKCC1 expression and activity through phosphorylation determined by the balance between kinase and protein phosphatase activities in the neuronal cells [25,50]. VPA has been shown to induce acetylation and demethylation in the test system, and VPA-induced histone acetylation and DNA demethylation have been shown to activate gene expression [32].…”

Section: Discussionmentioning

confidence: 99%

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Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Juknevičienė,

Balnytė,

Valančiūtė

et al. 2024

Biomedicines

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Valproic acid (VPA) has anticancer, anti-inflammatory, and epigenetic effects. The study aimed to determine the expression of carcinogenesis-related SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 in adult glioblastoma U87 MG and T98G cells and the effects of 0.5 mM, 0.75 mM, and 1.5 mM doses of VPA. RNA gene expression was determined by RT-PCR. GAPDH was used as a control. U87 and T98G control cells do not express SLC5A8 or CDH1. SLC12A5 was expressed in U87 control but not in T98G control cells. The SLC12A2 expression in the U87 control was significantly lower than in the T98G control. T98G control cells showed significantly higher CDH2 expression than U87 control cells. VPA treatment did not affect SLC12A2 expression in U87 cells, whereas treatment dose-dependently increased SLC12A2 expression in T98G cells. Treatment with 1.5 mM VPA induced SLC5A8 expression in U87 cells, while treatment of T98G cells with VPA did not affect SLC5A8 expression. Treatment of U87 cells with VPA significantly increased SLC12A5 expression. VPA increases CDH1 expression depending on the VPA dose. CDH2 expression was significantly increased only in the U87 1.5 mM VPA group. Tested VPA doses significantly increased CDH2 expression in T98G cells. When approaching treatment tactics, assessing the cell’s sensitivity to the agent is essential.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Juknevičienė,

Balnytė,

Valančiūtė

et al. 2024

Biomedicines

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Epigenetic Regulation of the Renin–Angiotensin–Aldosterone System in Hypertension

Takeda,

Demura,

Yoneda

et al. 2024

IJMS

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Activation of the renin–angiotensin–aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels of the angiotensinogen angiotensin-converting enzyme, angiotensin type 1 receptor gene, Agtr1a, and the aldosterone synthase gene, CYP11B2, have been reported in the heart, blood vessels, and kidneys in salt-sensitive hypertension. However, the mechanism of gene regulation in each component of the RAAS in cardiovascular and renal tissues is unclear. Epigenetic mechanisms, which are important for regulating gene expression, include DNA methylation, histone post-translational modifications, and microRNA (miRNA) regulation. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. Several miRNAs influence AGT expression and are associated with cardiovascular diseases. Expression of both ACE and ACE2 genes is regulated by DNA methylation, histone modifications, and miRNAs. Expression of both angiotensinogen and CYP11B2 is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. The mineralocorticoid receptor (MR) exists in cardiovascular and renal tissues, in which many miRNAs influence expression and contribute to the pathogenesis of hypertension. Expression of the 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene is also regulated by methylation and miRNAs. Epigenetic regulation of renal and vascular HSD11B2 is an important pathogenetic mechanism for salt-sensitive hypertension.

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DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development

Cited by 2 publications

References 73 publications

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Epigenetic Regulation of the Renin–Angiotensin–Aldosterone System in Hypertension

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