Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Dis Markers. 2020 Dec 7;2020:8861358. doi: 10.1155/2020/8861358. eCollection 2020.
The small musculoaponeurotic fibrosarcoma (sMaf) proteins MafF, MafG, and MafK are basic region leucine zipper- (bZIP-) type transcription factors and display tissue- or stimulus-specific expression patterns. As the oxidative stress reactive proteins, sMafs are implicated in various neurological disorders. In the present study, the expressions of sMafs were investigated across five databases gathering transcriptomic data from 74 Alzheimer's disease (AD) patients and 66 controls in the Gene Expression Omnibus (GEO) database. The expression of MafF was increased in the hippocampus of AD patients, which was negatively correlated with the expression of the glutamate cysteine ligase catalytic subunit (GCLC). Furthermore, MafF was significantly increased in patients with Braak stage V-VI, compared to those with Braak stage III-IV. -Amyloid (A), a strong inducer of oxidative stress, plays a crucial role in the pathogenesis of AD. The responsive expressions of sMafs to A-induced oxidative stress were studied in the APP/PS1 mouse model of AD, A intrahippocampal injection rats, and several human cell lines from different tissue origins. This study revealed that only the induction of MafF was accompanied with reduction of GCLC and glutathione (GSH). MafF knockdown suppressed the increase of GSH induced by A. Among sMafs, MafF is the most responsive to A-induced oxidative stress and might potentiate the inhibition of antioxidation. These results provide a better understanding of sMaf modulation in AD and highlight MafF as a potential therapeutic target in AD.
小肌肉腱膜纤维肉瘤 (sMaf) 蛋白 MafF、MafG 和 MafK 是碱性区域亮氨酸拉链-（bZIP-）型转录因子，具有组织或刺激特异性表达模式。作为氧化应激反应蛋白，sMafs 与各种神经疾病有关。在本研究中，通过 GEO 数据库中 74 名 AD 患者和 66 名对照的转录组数据，在五个数据库中研究了 sMafs 的表达。AD 患者海马区 MafF 的表达增加，与谷氨酸半胱氨酸连接酶催化亚基 (GCLC) 的表达呈负相关。此外，与 Braak 分期 III-IV 的患者相比，Braak 分期 V-VI 的患者 MafF 显著增加。β-淀粉样蛋白 (A)，一种强烈的氧化应激诱导物，在 AD 的发病机制中起着关键作用。在 AD 的 APP/PS1 小鼠模型、A 海马内注射大鼠和来自不同组织来源的几种人类细胞系中，研究了 sMafs 对 A 诱导的氧化应激的反应性表达。本研究表明，只有 MafF 的诱导伴随着 GCLC 和谷胱甘肽 (GSH) 的减少。MafF 敲低抑制了 A 诱导的 GSH 增加。在 sMafs 中，MafF 对 A 诱导的氧化应激最敏感，可能增强抗氧化抑制作用。这些结果提供了对 AD 中 sMaf 调节的更好理解，并强调了 MafF 作为 AD 潜在治疗靶点的潜力。
