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1.
J Cell Biochem ; 120(3): 3514-3519, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548663

RESUMO

A recent study has shown that early growth response 1 (EGR1) plays a critical role in the ß-amyloid cascade and tau hypotheses. In addition, evidence has suggested that EGR1 can regulate levels of amyloid-beta peptides, key molecules in the pathogenesis of Alzheimer's disease (AD). However, whether EGR1 is a deleterious or protective factor in the AD is still controversial. In this present study, we constructed an overexpression plasmid, CMV-EGFP-EGR1-Kanamycin, and transfected it into U87MG cells to investigate the effects of EGR1 expression on amyloid-ß (1-40) peptide (Aß40) levels. U87MG cells transfected by CMV-EGFP-EGR1-Kanamycin and CMV-EGFP-Kanamycin were assigned, respectively, to experimental and control groups. Fluorescence microscopy was used to observe transfection efficiencies of the plasmids after 6 hours. EGR1 messenger RNA levels were measured by quantitative reverse transcription polymerase chain reaction. Aß40 secretion was analyzed by enzyme-linked immunosorbent assay. Expression of the amyloid precursor protein, beta-secretase enzyme, and presenilin 1 proteins were analyzed by Western blot analysis. The results showed that EGR1 overexpression increased Aß40 secretion in vitro, possibly through increasing BACE1 expression. Based on these results, EGR1 might be a promising therapeutic target for the AD.


Assuntos
Secretases da Proteína Precursora do Amiloide/biossíntese , Peptídeos beta-Amiloides/metabolismo , Ácido Aspártico Endopeptidases/biossíntese , Proteína 1 de Resposta de Crescimento Precoce/biossíntese , Regulação Enzimológica da Expressão Gênica , Fragmentos de Peptídeos/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/genética , Ácido Aspártico Endopeptidases/genética , Linhagem Celular Tumoral , Proteína 1 de Resposta de Crescimento Precoce/genética , Humanos , Fragmentos de Peptídeos/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética
2.
J Stroke Cerebrovasc Dis ; 28(4): 1056-1061, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30658954

RESUMO

AIM: To investigate association of Apolipoprotein E (ApoE) gene promoter methylation with atherosclerotic cerebral infarction (ACI) in the Han Chinese population. METHODS: Twenty-six ACI patients (the case group) and 26 healthy (the control group) were recruited randomly from Henan Han nationality population, from April 2016 to August 2016. Bisulfite pyrosequencing technology was used to examine the role of the aberrant gene promoter methylation in ACI in Han Chinese population. Especially, we used the odds ratio and 95% confidence interval (95% CI) method to elevate the correlation between ApoE Promoter Methylation and ACI. RESULTS: The case group was significantly more likely to have hypertension and carotid atherosclerotic plaques (Table 1). The case group had significantly lower levels of high-density lipoprotein cholesterol (HDL-C), folate, and higher levels of homocysteine (Table 2). We observed that ACI patients (n = 26) had significantly higher methylation levels at cytosine-phosphate-guanine (CpG) 14 and CpG16 compared with controls (n = 26) (Table 3). Importantly, our results indicated a significant association between ApoE promoter methylation and ACI (OR = 16.146; 95% CI, 1.154-225.832; P* < .05; P*: adjusted for age, gender, carotid atherosclerotic plaque, hypertension, HDL-C, homocysteine, and folate) (Table 4). CONCLUSIONS: Our study indicates that ApoE promoter methylation may be associated with ACI in Han Chinese people.


Assuntos
Apolipoproteínas E/genética , Infarto Cerebral/genética , Metilação de DNA , Arteriosclerose Intracraniana/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Infarto Cerebral/sangue , Infarto Cerebral/diagnóstico , Infarto Cerebral/etnologia , China , Ilhas de CpG , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Arteriosclerose Intracraniana/sangue , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/etnologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Dados Preliminares , Medição de Risco , Fatores de Risco
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