缺氧条件下海马 CA3 区活性氧和自发荧光的变化:钙和锌流入的作用

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-10-15 DOI:10.1016/j.neuint.2024.105882
João L. Alves , Patrícia M. Reis , Rosa M. Quinta-Ferreira , M. Emília Quinta-Ferreira , Carlos M. Matias
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引用次数: 0

摘要

活性氧(ROS)在细胞生物学中发挥着重要作用,根据其含量参与细胞信号传导过程或氧化应激,可能与神经退行性疾病和其他疾病有关。大多数有关 ROS 形成的研究都是在缺血条件下进行的,因此对缺氧程度较轻条件下的 ROS 形成了解有限。本研究调查了缺氧条件下神经元 ROS 的生成和自发荧光的变化,重点关注钙和锌的参与。使用 Wistar 大鼠的海马切片,在不同氧合水平下通过渗透性荧光指示剂 H2DCFDA 监测 ROS 的产生。中度缺氧(40% O2)导致 ROS 少量增加,而严重缺氧(0% O2)则导致 ROS 明显增加。KCl 诱导的去极化显著增强了 ROS 的形成,尤其是在严重缺氧的情况下。抑制 NMDA 受体可减少 ROS 的产生,但不会影响自发荧光,而锌离子螯合可减少 ROS 的产生并增加黄素腺嘌呤二核苷酸(FAD)的自发荧光。这些发现表明,在缺氧条件下,ROS 的形成是通过 NMDA 受体的钙离子进入和锌离子流入介导的。因此,这些离子在氧化应激中起着至关重要的作用,而氧化应激可能与 ROS 失调相关的神经退行性疾病有关。
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Changes in reactive oxygen species and autofluorescence under hypoxia at the hippocampal CA3 area: Role of calcium and zinc influxes
Reactive oxygen species (ROS) have an important role in cellular biology, being involved, in a way that depends on their levels, in cell signaling processes or in oxidative stress, probably associated with neurodegenerative and other diseases. Most of the studies about ROS formation were performed in ischemic conditions, and thus, there is limited knowledge about ROS formation in less severe hypoxic conditions. This study investigates neuronal ROS generation and autofluorescence changes in hypoxic conditions, focusing on the involvement of calcium and zinc. Using hippocampal slices from Wistar rats, ROS production was monitored by the permeant fluorescent indicator H2DCFDA under different oxygenation levels. Moderate hypoxia (40% O2) led to a small ROS increase, while severe hypoxia (0% O2) showed a more pronounced rise. KCl-induced depolarization significantly enhanced ROS formation, particularly under severe hypoxia. Inhibition of NMDA receptors reduced ROS generation without affecting autofluorescence, while chelation of zinc ions decreased ROS production and increased flavin adenine dinucleotide (FAD) autofluorescence. These findings suggest that, in hypoxic conditions, ROS formation is mediated by calcium entry through NMDA receptors and also by zinc influxes. Thus, these ions play a crucial role in oxidative stress, which may be related with neurodegenerative diseases associated with ROS dysregulation.
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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