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miRNA-138 regulates MLK3/JNK/MAPK pathway to protect BV-2 cells from H2O2-induced apoptosis

R Ren, S D Chen, J Fan

    Bratislavske Lekarske Listy
    |May 12, 2018
    PubMed
    Abstract

    Insights

    MicroRNA-138 (miR-138) protects BV-2 cells from hydrogen peroxide-induced apoptosis by down-regulating Mixed Lineage Kinase 3 (MLK3) and inhibiting the JNK/MAPK pathway.

    Area of Science:

    • Neuroscience
    • Molecular Biology
    • Cell Biology

    Background:

    • MicroRNA-138 (miR-138) is downregulated in acute spinal cord injury.
    • Mixed lineage kinase 3 (MLK3) is a target of miR-138 and a key factor in the JNK/MAPK pathway.

    Purpose of the Study:

    • To investigate the role of miR-138 in hydrogen peroxide (H2O2)-induced apoptosis in BV-2 cells.
    • To elucidate the mechanism by which miR-138 affects the JNK/MAPK pathway.

    Main Methods:

    • BV-2 cells were treated with H2O2 to assess cell viability and miR-138 expression.
    • Cells were transfected with miR-138 agomir or antagomir.
    • Apoptosis was measured using Annexin V/PI staining.
    • Expression of miR-138, MLK3, and JNK/MAPK pathway components was analyzed.

    Main Results:

    • H2O2 treatment reduced cell viability and miR-138 expression.
    • Overexpression of miR-138 significantly decreased apoptosis (from 24.2% to 11.9%).
    • miR-138 overexpression downregulated JNK, p-JNK, c-jun, p-c-jun, p38 MAPK, p-p38 MAPK, iNOS, and COX-2.
    • Transfection with miR-138 antagomir yielded opposite effects.

    Conclusions:

    • miR-138 exhibits a protective effect against H2O2-induced apoptosis in BV-2 cells.
    • This protective effect is mediated by the downregulation of MLK3 and subsequent inhibition of the JNK/MAPK signaling pathway.
    Keywords:
    apoptosismiR-138microglia jun N-terminal kinase.mixed lineage kinase 3

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