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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Glutathione metabolism is modulated by postmortem interval, gender difference and agonal state in postmortem human brains
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Glutathione metabolism is modulated by postmortem interval, gender difference and agonal state in postmortem human brains

机译：谷胱甘肽代谢受人死后大脑中的死后间隔，性别差异和痛苦状态的调节

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摘要

The equilibrium between antioxidant function and oxidative stress is implicated in brain pathology. However, human studies on oxidant and antioxidant markers rely on postmortem tissue that might be affected by pre and postmortem factors. To evaluate the effect of these variables, we tested whether antioxidant enzymes [superoxide dismutase (SOD), catalase] glutathione (GSH) and related enzymes [gamma glutamylcysteine ligase (GCL), GSH peroxidase (GPx), GSH reductase (GR), GSH-S-transferase (GST)] and malondialdehyde (MDA, marker of lipid peroxidation) are affected in postmortem human brains (n = 50) by increase in postmortem interval (2.5-26 h), gender difference and agonal state [based on Glasgow coma scale (GCS): range: 3-15] in different anatomical regions-frontal cortex (FC), cerebellum (CB) medulla oblongata (MO), substantia nigra (SN) and hippocampus (HC). While SOD and catalase activities were relatively unaltered, GR and GPx activities were affected by agonal state (GR in CB, p < 0.05; GPx in MO, p < 0.05) indicating altered GSH dynamics during the secondary events following neuronal injury. MO, SN and HC displayed low GSH compared to FC and CB. Total GSH level was decreased with PMI (MO, p = 0.02) which could be partly attributed to increase in MDA levels with increasing PMI in MO (p < 0.05). Total GSH level was higher in CB (p < 0.017) and MO (p < 0.04) in female brains compared to males. Interestingly, HC and SN regions showed significant stability in most of the markers tested. We suggest that while SOD and catalase were relatively unaffected by the pre and postmortem factors, GSH and its metabolic enzymes were significantly altered and this was more pronounced in MO of postmortem human brains. These data highlight the influence of pre and postmortem factors on GSH dynamics and the inherent differences in brain regions, with implications for studies on brain pathophysiology employing human samples.
机译：抗氧化剂功能和氧化应激之间的平衡与脑病理学有关。但是，人类对氧化剂和抗氧化剂标记物的研究依赖于死后组织，这些组织可能会受到死前和死后因素的影响。为了评估这些变量的效果，我们测试了抗氧化酶[超氧化物歧化酶（SOD），过氧化氢酶]谷胱甘肽（GSH）和相关酶[γ谷氨酰半胱氨酸连接酶（GCL），GSH过氧化物酶（GPx），GSH还原酶（GR），GSH -S-转移酶（GST）]和丙二醛（MDA，脂质过氧化标记）在死后人类大脑（n = 50）中受到死后间隔时间（2.5-26 h），性别差异和精神状态的影响[基于格拉斯哥昏迷量表（GCS）：范围：3-15]在不同的解剖区域-额叶皮质（FC），小脑（CB）延髓（MO），黑质（SN）和海马（HC）。尽管SOD和过氧化氢酶的活性相对不变，但GR和GPx的活性受神经状态的影响（CB中的GR，p <0.05; MO中的GPx，p <0.05），表明神经元损伤继发事件期间GSH动力学改变。与FC和CB相比，MO，SN和HC的GSH较低。 PMI降低了总GSH水平（MO，p = 0.02），这可能部分归因于MO中PMI升高，MDA水平升高（p <0.05）。与男性相比，女性大脑中CB（p <0.017）和MO（p <0.04）的总GSH水平更高。有趣的是，HC和SN区在大多数测试标记中均显示出显着的稳定性。我们建议，虽然SOD和过氧化氢酶不受死前和死后因素的影响，但GSH及其代谢酶发生了显着变化，这在死后人脑的MO中更为明显。这些数据强调了死前和死后因素对GSH动力学的影响以及大脑区域的固有差异，这对使用人类样品进行脑病理生理学的研究具有重要意义。

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