Abstract:
:Genome-wide analysis of miRNA expression has revealed increased levels of miR-144 in the brains of Alzheimer's disease (AD) patients. Nuclear factor erythroid 2-related factor 2 (NRF2), a potential target of miR-144, is a central regulator of antioxidant response, and plays an important role in glutathione (GSH) biosynthesis and recycling. In this study, miR-144 mimic was used to over express miR-144. Aβ (1-42) was used to induce oxidative stress in SH-SY5Y cells. Cell viability and intracellular reactive oxygen species (ROS) were assessed to identify the effects of miR-144 on oxidative stress status. GSH and glutathion peroxidase (GPX) activities were detected to reveal the effect of miR-144 on GSH accumulation. To understand the effects of miR-144 on GSH biosynthesis and recycling, intracellular GPX1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GR), and NRF2 expression were detected by western blot and Real-time PCR. In oxidative stress conditions, miR-144 increased the intracellular accumulation of ROS, reduced cell viability, reduced the activities of GSH and antioxidant enzymes, GPX1, and decreased the expression of GCLC, GCLM, GR and NRF2. In conclusion, miR-144 modulates oxidative stress tolerance by regulating NRF2 expression and GSH generation, which may contribute to the pathogenesis of AD.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Zhou C,Zhao L,Zheng J,Wang K,Deng H,Liu P,Chen L,Mu Hdoi
10.1016/j.neulet.2017.06.045subject
Has Abstractpub_date
2017-08-10 00:00:00pages
21-27eissn
0304-3940issn
1872-7972pii
S0304-3940(17)30536-0journal_volume
655pub_type
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