NMDA受体
氧化应激
化学
内科学
受体
内分泌学
药理学
生物化学
生物
医学
作者
Patrycja Pańczyszyn-Trzewik,Paulina Misztak,Włodzimierz Opoka,Gabriel Nowak,Magdalena Sowa-Kućma
出处
期刊:PubMed
日期:2023-06-01
卷期号:74 (3)
被引量:1
标识
DOI:10.26402/jpp.2023.3.08
摘要
Suicide is a global public health concern. There is evidence of an association between suicidal behavior and depressive disorders (DDs). An increasing number of studies have suggested that nuclear factor erythroid-derived 2-like 2 (Nrf2), a major endogenous regulator of the oxidative stress response, can be a novel target for the neurobiology of suicide-related disorders (including depression). This study aimed to investigate the relationship between oxidative stress progression, Nrf2 regulation, and N-methyl-D-aspartate receptor (NMDA) subunit composition in the hippocampus (Hp) and frontal cortex (FCx) of suicide victims (n=14) and matched controls (n=8). Furthermore, zinc and magnesium concentrations and their potency to inhibit [3H] MK-801 (radioactively labeled form of MK-801 - dizocilpine, a well-characterized NMDAR channel uncompetitive antagonist frequently used in receptor-binding assays) binding to NMDA receptor channels were measured. Our results revealed a statistically significant increase in protein carbonyl levels and thiobarbituric acid-reactive substances (TBARS) concentrations in Hp and FCx of suicide victims. Enhanced superoxide dismutase (SOD) activity (only in FCx) in suicides compared to controls was shown. These alterations were accompanied by an increase in Nrf2 protein levels in whole homogeneous tissue lysates and cytosolic fractions of Hp and FCx. Importantly, suicide victims presented a significant reduction in Nrf2 protein levels in the nuclear fraction of FCx. Finally, the observed decrease in N-methyl-D-aspartate receptor subunit 2B (GluN2B) and postsynaptic density proteins 95 (PSD-95) protein levels was associated with a statistically significant reduction in magnesium levels in the FCx of suicide victims. These results confirm for the first time that increased oxidative stress parameters are related to Nrf2 protein changes and alterations in the NMDA receptor complex in the pathophysiology of suicidal behavior.
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