甲基氨酸的错误整合和依赖氧化还原的电压通通道功能的增益
Rama A Hussein1, Marwa Ahmed1, Stefan H Heinemann1
1Center for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University Jena and Jena University Hospital, Jena, Germany.
Journal of neurochemistry
|September 8, 2023
概括
甲 (SeMet) 融入通道 (NaV) 使它们对氧化应激敏感,从而损害了快速不活化. 这种SeMet效应可能会导致心律失常和神经病变.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 甲 (SeMet) 可以替代蛋白质中的甲 (Met),随着饮食摄入而积累.
- 在电压通道 (NaV) 中的Met残留物的氧化会损害快速无活化,这对于作用潜力的形成至关重要.
- 错误纳入SeMet对NaV通道功能和电刺激性的影响在很大程度上是未知的.
研究的目的:
- 调查SeMet错误纳入NaV通道的功能后果.
- 为了确定SeMet是否会影响NaV通道对氧化应激的敏感性.
- 探索SeMet在NaV通道相关病理中的潜在作用.
主要方法:
- 将SeMet纳入重新组合的老鼠和人类NaV通道亚型 (NaV1.4,1.2,1.5,1.7).
- 电生理学记录以评估通道功能,无活化和电流密度.
- 暴露小鼠背部根结质神经元 (DRG) 的SeMet和氧化应激.
主要成果:
- 广泛将SeMet纳入NaV1.4通道并没有改变基底功能,但增加了对氧化应激的敏感性,导致失活和最大电流的减少.
- 这些效应是可逆的与dithiothreitol (DDT) 减少,表明SeMet氧化作用.
- 在DRG神经元中的SeMet暴露加剧了氧化诱导的作用潜力的扩大和持续的NaV电流的增加.
结论:
- 将SeMet错误地纳入NaV通道使它们对氧化侮辱敏感,导致快速失活.
- 这种SeMet诱导的通道功能障碍可能会导致心律失常和神经病变等过度兴奋性障碍.
- 这些发现凸显了SeMet积累在氧化应激背景下的潜在临床相关性.
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