Page 59 - Q. Neuroscience

Protective role of ABCA1 in ischemic preconditioning is mediated by
downregulation of miR-33-5p and miR-135-5p

Jung-Hyuck Ahn
Department of Biochemistry, College of Medicine, Ewha Womans University

BACKGROUND AIM

Ischemic preconditioning (IPC) significantly reduces ischemia- To elucidate exact mechanisms of neuroprotection mediated
reperfusion injury in the brain by inducing ischemic tolerance. by IPC, we investigated the miRNA expression patterns
Although emerging evidence suggests that microRNAs (miRNAs) after IPC in cerebral ischemia models and identified
contribute to the pathogenesis of brain ischemia and IPC- neuroprotective miRNAs and their targets.
induced neuroprotection, the role of miRNAs and their
underlying mechanisms are still unclear.
preconditioning (IPC) METHODS
(n=2 to 4/group). During surgery, the reduction of cerebral blood flow was monitored by using Laser Doppler Flowmetry secured
Ischemic preconditioning
for 1 minute was induced at three times in mice by
intraluminal thread occlusion of the middle cerebral artery.
Middle cerebral artery occlusion (MACO) was performed Briefly, a monofilament
was introduced into the left common carotid artery under halothane anesthesia,
advance to the origin of the middle cerebral artery (MCA) and left for 30mins until
reperfusion (n=2 to 4/group). During surgery, the reduction of cerebral blood flow was
monitored by using Laser Doppler Flowmetry secured to the left temporal skull
surface and the rectal temperature was maintained at 37.0±0.5 C. Mice were killed
o
after 3 hours reperfusion.
RESULTS

Figure 3. Identification Figure 3.
of Abca1 mRNA as a Identification of

target for miR-33-5p Abca1 mRNA as a

and miR-135b-5p. target for miR-33-

Figure 1. Changes to Bax/Bcl2 ratios in 5p and miR-135b-
ischemic cortex.
Figure 2. 5p.
Neuroprotective

effects by

downregulation of
miR-33-5p and miR-

135b-5p. Figure 3. Identification of Abca1 mRNA
as a target for miR-33-5p and miR-
135b-5p. Figure 4. ABCA1 suppresses a
mitochondria-dependent
Figure 2. Neuroprotective effects by apoptosis pathway.
downregulation of miR-33-5p and miR-
135b-5p.
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

Increased ABCA1 expression This research was supported by a grant
expression
ABCA1
Increased
following IPC exerts a protective • Rink C, Khanna S (2011) Physoiol of the Korea Health Technology R&D
following IPC exerts a protective
effect against cerebral ischemia via Genomics 43. 521-528 Project through KHIDI, funded by the
effect against cerebral ischemia via
suppression of a mitochondria- • Lee S, Chu K, Jung K, Yoon H, Jeon Ministry of Health & Welfare, Republic of
mitochondria-
of
suppression
a
dependent apoptosis pathway. The D, Kang K, Park K, Bae E, Kim M, Korea (grant number: HI18C0460)
dependent apoptosis pathway. The
regulatory mechanisms for both Lee SK, Roh J (2010) Stroke 41.
regulatory mechanisms for both miR-
miR-33-5p and miR-135b-5p on 1646-1651
33-5p and miR-135b-5p on ABCA1
ABCA1 expression may provide • Saugstad JA (2015) Frontier in Contact information
expression may provide potential
potential therapeutic targets for neurology 6. 1-11
therapeutic targets for treating stroke.
treating stroke Email: ahnj@ewha.ac.kr
Telephone : +82-2-6986-6200