Blockade of HCN2 Channels Provides Neuroprotection Against Ischemic Injury via Accelerating Autophagic Degradation in Hippocampal Neurons.

Neuroscience Bulletin
Cheng ChenChang-Jun Li

Abstract

In the central nervous system, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential to maintain normal neuronal function. Recent studies have shown that HCN channels may be involved in the pathological process of ischemic brain injury, but the mechanisms remain unclear. Autophagy is activated in cerebral ischemia, but its role in cell death/survival remains controversial. In this study, our results showed that the HCN channel blocker ZD7288 remarkably decreased the percentage of apoptotic neurons and corrected the excessive autophagy induced by oxygen-glucose deprivation followed by reperfusion (OGD/R) in hippocampal HT22 neurons. Furthermore, in the OGD/R group, p-mTOR, p-ULK1 (Ser757), and p62 were significantly decreased, while p-ULK1 (Ser317), atg5, and beclin1 were remarkably increased. ZD7288 did not change the expression of p-ULK1 (Ser757), ULK1 (Ser317), p62, Beclin1, and atg5, which are involved in regulating autophagosome formation. Besides, we found that OGD/R induced a significant increase in Cathepsin D expression, but not LAMP-1. Treatment with ZD7288 at 10 μmol/L in the OGD/R group did not change the expression of cathepsin D and LAMP-1. However, chloroquine (CQ), which decreases autop...Continue Reading

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Citations

Dec 3, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Zhiqiang GaoYunxia Wu
Jun 22, 2021·Frontiers in Molecular Neuroscience·Deepanjali Dwivedi, Upinder S Bhalla

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Methods Mentioned

BETA
transfection
ELISA
fluorescence-activated cell sorting
Protein Assay
light microscopy
flow cytometry
ubiquitination

Software Mentioned

ImageJ
BD FACSDiva
NIH ImageJ
SPSS

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