Involvement of Promyelocytic Leukemia Protein in the Ethanol-induced Apoptosis in Mouse Embryo Fibroblasts

Wang, Lihui; Yang, Jingyu; Cui, Wei; Shin, Young Kee; Wu, Chunfu

doi:10.1248/yakushi.128.1067

Cited by 4 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite this observation, and consistent with our data, the Dnmt-1 transcript was down-regulated by alcohol in both neural stem cells [60] and rat sperm [61]. Numerous studies have reported the effects of ethanol exposure on gene expression [29,62–69]. Intriguingly, in the present study, ethanol stimulated the expression of the genes encoding the “ de novo ” methyltransferases (DNMT-3a and -3b), but not the “maintenance” methyltransferase (DNMT-1).…”

Section: Discussionsupporting

confidence: 88%

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Mukhopadhyay

Rezzoug

Kaikaus

et al. 2013

Reproductive Toxicology

View full text Add to dashboard Cite

Fetal alcohol syndrome (FAS), presenting with a constellation of neuro-/psychological, craniofacial and cardiac abnormalities, occurs frequently in offspring of women who consume alcohol during pregnancy, with a prevalence of 1–3 per 1000 livebirths. The present study was designed to test the hypothesis that alcohol alters global DNA methylation, and modulates expression of the DNA methyltransferases (DNMTs) and various methyl CpG-binding proteins. Murine embryonic fibroblasts (MEFs), utilized as an in vitro embryonic model system, demonstrated ~5% reduction in global DNA methylation following exposure to 200 mM ethanol. In addition, ethanol induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Such degradation could be completely rescued by pretreatment of MEF cells with the proteasomal inhibitor, MG-132. These data support a potential epigenetic molecular mechanism underlying the pathogenesis of FAS during mammalian development.

show abstract

Section: Discussionsupporting

confidence: 88%

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Mukhopadhyay

Rezzoug

Kaikaus

et al. 2013

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…However, these results do suggest that in MEFs that the Plk4 promoter may be a target for regulation by methylation in response to metabolic stress. This idea is supported by the fact that chronic alcohol exposure of MEFs has been shown to increase levels of reactive oxygen species (ROS) [30], as well as increase levels of p53 and p53 downstream targets such as p21 [31]. Interestingly, consistent with this p53 has been shown to indirectly repress Plk4 expression via HDAC in response to stress [22].…”

Section: Resultsmentioning

confidence: 97%

Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

et al. 2011

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC), one of the most common cancers world-wide occurs twice as often in men compared to women. Predisposing conditions such as alcoholism, chronic viral hepatitis, aflatoxin B1 ingestion, and cirrhosis all contribute to the development of HCC.MethodsWe used a combination of methylation specific PCR and bisulfite sequencing, qReal-Time PCR (qPCR), and Western blot analysis to examine epigenetic changes for the Polo-like kinases (Plks) during the development of hepatocellular carcinoma (HCC) in Plk4 heterozygous mice and murine embryonic fibroblasts (MEFs).ResultsHere we report that the promoter methylation of Plk4 CpG islands increases with age, was more prevalent in males and that Plk4 epigenetic modification and subsequent downregulation of expression was associated with the development of HCC in Plk4 mutant mice. Interestingly, the opposite occurs with another Plk family member, Plk1 which was typically hypermethylated in normal liver tissue but became hypomethylated and upregulated in liver tumours. Furthermore, upon alcohol exposure murine embryonic fibroblasts exhibited increased Plk4 hypermethylation and downregulation along with increased centrosome numbers and multinucleation.ConclusionsThese results suggest that aberrant Plk methylation is correlated with the development of HCC in mice.

show abstract

“…There are a number of discrepancies in the literature regarding the response of cells to EtOH, particularly regarding cell proliferation and apoptosis. Studies with fibroblasts isolated from skin and mouse embryos have reported decreases in proliferation and apoptosis when exposed to EtOH (Ranzer et al., ; Wang et al., ). The amount of EtOH used for treatment may be important as well as the origin of the fibroblasts as another study utilizing embryonic fibroblasts and a smaller concentration of EtOH reported no apoptosis or fibrogenic effects caused by EtOH alone (Brenner and Chojkier, ).…”

Section: Discussionmentioning

confidence: 99%

Activation of Cardiac Fibroblasts by Ethanol Is Blocked by TGF‐β Inhibition

Law

Carver

2013

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

Background Alcohol abuse is the second leading cause of dilated cardiomyopathy, a disorder specifically referred to as Alcoholic Cardiomyopathy (ACM). Rodent and human studies have revealed cardiac fibrosis to be a consequence of ACM and prior studies by this lab have associated this occurrence with elevated transforming growth factor-beta (TGF-β) and activated fibroblasts (myofibroblasts). To date there have been no other studies to investigate the direct effect of alcohol on the cardiac fibroblast. Methods Primary rat cardiac fibroblasts were cultured in the presence of ethanol and assayed for fibroblast activation by collagen gel contraction, alpha smooth muscle- actin (α-SMA) expression, migration, proliferation, apoptosis, collagen I & III and TGF-β expression. The TGF-β receptor type 1 inhibitor compound SB 431542 and a soluble recombinant TGF-βII receptor (RbII) were used to assess the role of of TGF-β in the response of cardiac fibroblasts to ethanol. Results Treatment of cardiac fibroblasts with ethanol at concentrations of 100 mg/dl or higher resulted in fibroblast activation and fibrogenic activity after 24 hours including an increase in contraction, α-SMA expression, migration, and expression of collagen I and TGF-β. No changes in fibroblast proliferation or apoptosis were observed. Inhibition of TGF-β by SB 431542 and RbII attenuated the ethanol-induced fibroblast activation. Conclusions Ethanol treatment directly promotes cardiac fibroblast activation by stimulating TGF-β release from fibroblasts. Inhibiting the action of TGF-β decreases the fibrogenic effect induced by ethanol treatment. The results of this study support TGF-β to be an important component in cardiac fibrosis induced by exposure to ethanol.

show abstract

Involvement of Promyelocytic Leukemia Protein in the Ethanol-induced Apoptosis in Mouse Embryo Fibroblasts

Cited by 4 publications

References 18 publications

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

Activation of Cardiac Fibroblasts by Ethanol Is Blocked by TGF‐β Inhibition

Contact Info

Product

Resources

About