Oncotarget

Research Papers:

PKC and CaMK-II inhibitions coordinately rescue ischemia-induced GABAergic neuron dysfunction

Li Huang, Chun Wang, Shidi Zhao, Rongjing Ge, Sudong Guan and Jin-Hui Wang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:39309-39322. https://doi.org/10.18632/oncotarget.16947

Metrics: PDF 1008 views  |   HTML 1330 views  |   ?  


Abstract

Li Huang1,*, Chun Wang2,*, Shidi Zhao1,*, Rongjing Ge1, Sudong Guan1 and Jin-Hui Wang1,3

1Department of Pathophysiology, Bengbu Medical College, Bengbu 233000, China

2Department of Endocrinology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233040, China

3Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

*These authors have contributed equally to this work

Correspondence to:

Jin-Hui Wang, email: jhw@ibp.ac.cn

Keywords: ischemia, GABA, neuron, synapse, PKC and CaMK-II

Received: February 17, 2017    Accepted: March 15, 2017    Published: April 07, 2017

ABSTRACT

Cerebral ischemia leads to neuronal death for stroke, in which the imbalance between glutamatergic neurons and GABAergic neurons toward neural excitotoxicity is presumably involved. GABAergic neurons are vulnerable to pathological factors and impaired in an early stage of ischemia. The rescue of GABAergic neurons is expected to be the strategy to reserve ischemic neuronal impairment. As protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMK-II) are activated during ischemia, we have investigated whether the inhibitions of these kinases rescue the ischemic impairment of cortical GABAergic neurons. The functions of GABAergic neurons were analyzed by whole-cell recording in the cortical slices during ischemia and in presence of 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (CaMK-II inhibitor) and chelerythrine chloride (PKC inhibitor). Our results indicate that PKC inhibitor or CaMK-II inhibitor partially prevents ischemia-induced functional deficits of cortical GABAergic neurons. Moreover, the combination of PKC and CaMK-II inhibitors synergistically reverses this ischemia-induced deficit of GABAergic neurons. One of potential therapeutic strategies for ischemic stroke may be to rescue the ischemia-induced deficit of cortical GABAergic neurons by inhibiting PKC and CaMK-II.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 16947