MiR-29 Targets PUMA to Suppress Oxygen and Glucose Deprivation/Reperfusion (OGD/R)-induced Cell Death in Hippocampal Neurons

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*Fang Chen*

Affiliation:

• Department of Cardiothoracic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062,China

• Department of Urologic Surgery, Shanghai Children`s Hospital, Shanghai Jiao Tong University, NO. 355, Luding Road, Shanghai, 200062,China

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.

Cite this article as:

Wei Rong , Zhang Rufang , Li Hongmei , Li Hongyun , Zhang Saiji, Xie Yewei , Shen Li *, Chen Fang *, MiR-29 Targets PUMA to Suppress Oxygen and Glucose Deprivation/Reperfusion (OGD/R)-induced Cell Death in Hippocampal Neurons, Current Neurovascular Research 2018; 15 (1) . https://dx.doi.org/10.2174/1567202615666180403170902