内皮一氧化氮合酶单倍型对一氧化氮和过氧化亚硝酸盐生成的影响

IF 4.8 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioelectrochemistry Pub Date : 2024-10-16 DOI:10.1016/j.bioelechem.2024.108837

Seham O. Alsulami , Tadeusz Malinski , Howard D. Dewald

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引用次数: 0

摘要

内皮一氧化氮合酶（eNOS）多态性的四种具有临床意义的基因变异对一氧化氮[NO]和过氧化亚硝酸盐[ONOO-]浓度的影响一直鲜有研究。本研究利用[NO]/[ONOO-]比值来确定这些 eNOS 基因变异引起的内皮功能障碍的程度。利用桑格测序法和 DNA 电泳法分别对人脐静脉内皮细胞（HUVEC）中的单核苷酸多态性（T-786C、C-665T 和 Glu298Asp）和可变串联重复序列（内含子 4 a/b/c）进行了基因分型。纳米传感器用于测定最大[NO]和[ONOO-]，传统SDS-PAGE和低温SDS-PAGE分别用于评估eNOS的表达和eNOS二聚体与单体的比例。研究结果表明，当[NO]/[ONOO-]比值高于2时，eNOS单倍型H3（G T/C C 4a/c等位基因）可能对心血管疾病（CVD）有保护作用。研究结果表明，某些 eNOS 单倍型 H2（G T/C C 4a/b）和 H5（T T/C C 4b）可能会增加对[NO]/[ONOO-]比值低于 1 的心血管疾病的易感性。

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Influence of endothelial nitric oxide synthase haplotypes on nitric oxide and peroxynitrite productions

The impact of four clinically significant genetic variants of endothelial nitric oxide synthase (eNOS) polymorphisms on the concentrations of nitric oxide [NO] and peroxynitrite [ONOO^–] has been given scant consideration. This study utilized a [NO]/[ONOO^–] ratio to determine the extent of endothelial dysfunction caused by these variations in the eNOS gene. The single nucleotide polymorphisms (T-786C, C-665T, and Glu298Asp) and a variable number of tandem repeats (intron 4 a/b/c) were genotyped in human umbilical vein endothelial cells (HUVEC), using sanger sequencing and DNA electrophoresis, respectively. Nanosensors were used to determine the maximal [NO] and [ONOO^–], while traditional and low-temperature SDS-PAGE were used to evaluate the expression of eNOS and the eNOS dimer-to-monomer ratio, respectively. The study results indicate that the eNOS haplotype H3 (G T/C C 4a/c allele) may have a protective effect against cardiovascular disease (CVD) with the [NO]/[ONOO^–] ratio higher than 2. However, the eNOS haplotypes H2 (G T/C C 4a/b) and H5 (T T/C C 4b) increase the susceptibility to CVD with [NO]/[ONOO^–] ratio lower than 1. The results suggest that certain eNOS genetic variants may influence susceptibility to cardiovascular disease (CVD) while other variants may have a protective effect.

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来源期刊

Bioelectrochemistry 生物-电化学

CiteScore

9.10

自引率

6.00%

发文量

238

审稿时长

38 days

期刊介绍： An International Journal Devoted to Electrochemical Aspects of Biology and Biological Aspects of Electrochemistry Bioelectrochemistry is an international journal devoted to electrochemical principles in biology and biological aspects of electrochemistry. It publishes experimental and theoretical papers dealing with the electrochemical aspects of: • Electrified interfaces (electric double layers, adsorption, electron transfer, protein electrochemistry, basic principles of biosensors, biosensor interfaces and bio-nanosensor design and construction. • Electric and magnetic field effects (field-dependent processes, field interactions with molecules, intramolecular field effects, sensory systems for electric and magnetic fields, molecular and cellular mechanisms) • Bioenergetics and signal transduction (energy conversion, photosynthetic and visual membranes) • Biomembranes and model membranes (thermodynamics and mechanics, membrane transport, electroporation, fusion and insertion) • Electrochemical applications in medicine and biotechnology (drug delivery and gene transfer to cells and tissues, iontophoresis, skin electroporation, injury and repair). • Organization and use of arrays in-vitro and in-vivo, including as part of feedback control. • Electrochemical interrogation of biofilms as generated by microorganisms and tissue reaction associated with medical implants.