Page 60 - Q. Neuroscience

[Q. Neuroscience-36]

Protective role of ABCA1 in ischemic preconditioning is

mediated by downregulation of miR-33-5p and miR-135-5p

Jung-Hyuck Ahn¹

¹Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, Korea

Ischemic preconditioning (IPC) significantly reduces ischemia-reperfusion injury in the brain by inducing ischemic
tolerance. Although emerging evidence suggests that miRNAs contribute to the pathogenesis of brain ischemia and
IPC-induced neuroprotection, the role of miRNAs and their underlying mechanisms are still unclear. Post-IPC miRNA

expression profiling identified neuroprotection-associated changes in miRNA expression in the ipsilateral cortex

after ischemic stroke. Among them, miR-33-5p and miR-135b-5p were significantly downregulated by IPC. Inhibition
of miR-33-5p and miR-135b-5p expression protected Neuro-2a cells from OGD-induced apoptosis. Inhibition of
these two miRNAs significantly increased mRNA and protein levels of ABCA1, and a binding assay showed that

these two miRNAs showed specificity for Abca1 mRNA. Overexpression of ABCA1 decreased the Bax/Bcl2 mRNA
ratio and activation of caspase-9 and caspase-3, whereas knockdown of ABCA1 expression increased the Bax/Bcl2

mRNA ratio and the percentage of Neuro-2a cells with a loss of mitochondrial membrane potential after OGD-
treatment. Increased ABCA1 expression following IPC exerts a protective influence against cerebral ischemia via

suppression of a mitochondria-dependent apoptosis pathway.