Hyperhomocysteinemia-mediated DNA Hypomethylation and its Potential Epigenetic Role in Rats

Jiang, Yideng; Sun, Tongwen; Xiong, Jiantuan; Cao, Ji; Li, Guizhong; Wang, Shuren

doi:10.1111/j.1745-7270.2007.00327.x

Cited by 69 publications

(42 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the exact molecular mechanisms remain to be elucidated. In our previous study, Hcy was found to be involved in the disturbance of the expression of the LDL-receptor promoter region and global genome DNA hypomethylation through the interference of DNA methylation (25)(26)(27). Increasing evidence also suggests that aberrant DNA methylation around promoter regions can lead to the development of AS (28).…”

Section: Discussionmentioning

confidence: 99%

FABP4-mediated homocysteine-induced cholesterol accumulation in THP-1 monocyte-derived macrophages and the potential epigenetic mechanism

Jiang

Zhang

et al. 2016

Molecular Medicine Reports

Self Cite

View full text Add to dashboard Cite

Abstract. Hyperhomocysteinemia (HHcy) is an independent risk factor for the development of atherosclerosis (AS), according to overwhelming number of clinical and epidemiological studies. However, the underlying pathogenic molecular mechanisms by which HHcy promotes AS remain to be fully elucidated. Fatty acid binding protein 4 (FABP4) has been shown to be important in macrophage cholesterol trafficking. The objective of the present study was to determine whether homocysteine (Hcy) accelerates AS through regulating FABP4, and then mediates cholesterol accumulation in macrophages. Hcy concentrations of 0, 50, 100, 200 and 500 µM, and 100 µM Hcy+30 µM vitamin B 12 (VB 12 )+30 µM folic acid (FA) were respectively added to cultured THP-1 monocyte-derived macrophages for 24 h. The levels of FABP4, which acts as a key factor connecting cellular lipid accumulation to inflammation, were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in the macrophages. The present study used a nested touchdown methylation-specific PCR assay to detect the DNA methylation status of the FABP4 promoter region. In addition, the FABP4 gene fragment was inserted into the cloning vector, pcDNA3.1-EGFP, to construct the recombinant plasmid, pcDNA3.1-EGFP/FABP4, which was identified using restriction endonuclease digestion analysis and DNA sequencing. The pcDNA3.1-EGFP/FABP4 expression plasmid was transfected into THP-1 monocyte-derived macrophages, mediated by liposome reagent, following which the expression levels of FABP4 were detected using RT-qPCR and western blot analyses. The present study also determined the intracellular accumulation of total cholesterol in the macrophages. The results indicated that Hcy decreased the levels of FABP4 promoter methylation, but increased the mRNA and protein expression levels of FABP4 in the macrophages, compared with the control group (0 µM Hcy). However, no dose-dependent changes were observed with increasing concentrations of Hcy. The recombinant fluorescent eukaryotic expression vector, pcDNA3.1-EGFP/FABP4, was successfully constructed and effectively expressed in the THP-1 macrophages. The results also showed that FABP4 accelerated the accumulation of cholesterol in the macrophages. Taken together, the results of the present study suggested that FABP4 DNA hypomethylation induced by Hcy may be involved in the overexpression of FABP4, thereby inducing cholesterol accumulation in macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

FABP4-mediated homocysteine-induced cholesterol accumulation in THP-1 monocyte-derived macrophages and the potential epigenetic mechanism

Jiang

Zhang

et al. 2016

Molecular Medicine Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, deprived intake of essential nutrition, which supply the methyl groups from methyl folate or vitamin B12 and cause hyperhomocysteinemia or high level of tHcy.HHcy in depression indicates a breakdown in the methylation of homocysteine to methionine or cysteine, taurine, and glutathione -a B6 -dependent process and causes oxidative stress resulting in neurological and vascular damage and lead to disturbance in the optimal biosynthesis of neurotransmitters and cell signalling or cell repair and also disturbed the level of MAO in brain, its higher concentration as neurotoxic [24]. It is associated with various cardiovascular and other neurologicaldisorders, including cognitive impairment and dementia conversely, accumulation of tHcy involved in the path physiology of depression and reduces the level of neurotransmitters such as serotonin, dopamine, noradrenalin, and γ aminobutyric acid (GABA) are often associated with depression [10,[12][13][14]25,[32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and DNA hypomethylation, reduced the monoamines synthesis in depression: A case control study

Kumari¹,

Agrawal²,

Singh³

et al. 2015

J Integr Syst Neurosci

View full text Add to dashboard Cite

show abstract

“…A series of studies has shown that elevation of plasma Hcy correlates with increased AdoHcy levels and with a decreased MP [16]. The low MP is associated with a decreased global DNA methylation [17,18] and these epigenetic changes can lead to inappropriate gene expression and promotion of disease [19,20]. However, a case of AdoHcy-hydrolase deficiency was reported in which the patient's leukocyte DNA was hypermethylated relative to controls despite extremely high levels of plasma AdoHcy [21].…”

Section: Introductionmentioning

confidence: 99%

Hyperhomocysteinemia is Associated with Decreased Erythropoietin Expression in Rats

Grenz

Hermes

Hammel

et al. 2010

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Elevated plasma homocysteine (Hcy) levels have been identified as a pathogenic factor causing a variety of pathological changes in different cells and tissues. In vertebrates, Hcy is produced solely from S-adenosylhomocysteine (AdoHcy) through the catalysis of AdoHcy-hydrolase. The direction of AdoHcy-hydrolase activity is determined by its cytosolic substrate concentrations, thereby controlling intracellular AdoHcy levels. Most S-adenosylmethionine (AdoMet)-dependent methyltransferases are regulated in vivo by the ratio of AdoMet/AdoHcy, which is termed “methylation potential” (MP). To test whether high rates of erythropoietin (EPO) expression is reduced by a low MP in vivo we choosed the model of increased EPO production following carbon monoxide (CO) exposure in rats in which high transcriptional activity is responsible for renal EPO production. Results: To induce a sustained hyperhomocysteinemia in rats, we infused i.v. a low or high dose of Hcy resulting in Hcy plasma levels of 87.4±6.2 and 300.8±23.7 µmol/l, respectively. Renal tissue contents of AdoHcy, AdoMet, and adenosine (Ado) were measured after freeze clamp by means of HPLC. Within 4h of CO exposure EPO serum levels increased from 13.6±0.4 (control) to 2254.8±278.3 mIU/ml. Only high dose of Hcy reduces both, the MP from 40.8±2.0 to 8.2±1.0 in the kidney as well as EPO serum levels by 40% compared to control rats. Conclusion: Our data show that severe hyperhomocysteinemia (HHcy) affects the MP in the renal tissue and lowers EPO expression following CO induced intoxication. This result supports the concept that efficient EPO production requires an unimpaired MP.

show abstract

Hyperhomocysteinemia-mediated DNA Hypomethylation and its Potential Epigenetic Role in Rats

Cited by 69 publications

References 43 publications

FABP4-mediated homocysteine-induced cholesterol accumulation in THP-1 monocyte-derived macrophages and the potential epigenetic mechanism

FABP4-mediated homocysteine-induced cholesterol accumulation in THP-1 monocyte-derived macrophages and the potential epigenetic mechanism

Hyperhomocysteinemia and DNA hypomethylation, reduced the monoamines synthesis in depression: A case control study

Hyperhomocysteinemia is Associated with Decreased Erythropoietin Expression in Rats

Contact Info

Product

Resources

About