Title:MiR-29 Targets PUMA to Suppress Oxygen and Glucose Deprivation/Reperfusion (OGD/R)-induced Cell Death in Hippocampal Neurons
VOLUME: 15 ISSUE: 1
Author(s):Rong Wei, Rufang Zhang, Hongmei Li, Hongyun Li, Saiji Zhang, Yewei Xie, Li Shen* and Fang Chen*
Affiliation:Department of Anesthesiology, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Cardiothoracic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Cardiothoracic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Anesthesiology, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Anesthesiology, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Cardiothoracic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Cardiothoracic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062, Department of Urologic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062
Keywords:DHCA, miRNA, oxidative stress, apoptosis, PUMA, Reactive Oxygen Species (ROS).
Abstract:Introduction: We previously demonstrated that microRNAs (miRNA) play an important
role in Hypothermic Circulatory Arrest (DHCA)-associated neural injury. However, the specific
role of miRNAs in the pathogenesis of DHCA-induced neuron death is still unclear.
Material and Methods: Thus, in the present study, we investigated miR-29 expression and roles in
neuronal HT-22 cells with Oxygen-glucose Deprivation/reoxygenation (OGD/R). In this study, the
model of OGD/R was established using an airtight culture container and the anaeropack. Measurement
of Reactive Oxygen Species (ROS) production and Mitochondrial Membrane Potential
(MMP) was done using the probes of JC-1 and H2DCFDA. The microRNA (miRNA) profile in
hippocampal neurons from rat model of DHCA was determined by miRNA deep sequencing.
Results: We found that the expression of the miR-29 family (miR-29a/b/c) was significantly reduced
in model of DHCA and OGD/R. Overexpression of the miR-29 family inhibited the
OGD/R-induced elevation of ROS and reduction of MMP in HT-22 cells. In addition, administration
of the miR-29 family suppressed proteins of Keap1, Bax and PUMA and increased Nrf2 expression.
We further demonstrated that the miR-29 family targeted the PUMA by luciferase reporter
assay and Western blot analysis.
Conclusion: In conclusion, our data suggest that by targeting a pro-apoptotic BCL2 family member
PUMA, the miR-29 family might emerge as a strategy for protection against DHCA-mediated
neural cell injury.
