Inhibitions of PKC and CaMK-II synergistically rescue ischemia-induced astrocytic dysfunction.

Abstract

Ischemic neuronal death is presumably caused by glutamate-induced excitotoxicity, in which the increased glutamate release and impaired glutamate reuptake lead to glutamate accumulation. Mechanisms underlying the ischemic deficiency of astrocytic glutamate reuptake remain unclear, which we have studied by analyzing the effect of calmodulin-dependent protein kinase II (CaMK-II) and protein kinase C (PKC) inhibitions on astrocytic glutamate transporter during ischemia. Glutamate transporter current was recorded on the astrocytes in cortical slices. KN-62 (CaMK-II inhibitor) or chelerythrine (PKC inhibitor) partially reverses the ischemic deficiency of astrocytic glutamate transporter. A combined use of PKC and CaMK-II inhibitors synergistically reverses this deficiency. Thus, one of potential therapeutic strategies is to secure the ischemia-induced deficiency of astrocytic glutamate reuptake by inhibiting PKC and CaMK-II.

• Authors: Zhan Liu, Ying Huang, Lina Liu, Li Zhang
• Journal: Neuroscience letters (Neurosci Lett) Vol. 657 Pg. 199-203 (Sep 14 2017) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 28811196 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Amino Acid Transport System X-AG
• Protein Kinase Inhibitors
• Protein Kinase C
• Calcium-Calmodulin-Dependent Protein Kinase Type 2

Topics

• Amino Acid Transport System X-AG (drug effects)
• Animals
• Astrocytes (drug effects, metabolism, pathology)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (antagonists & inhibitors)
• Cell Death (drug effects)
• Cerebral Cortex (drug effects, metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Protein Kinase C (antagonists & inhibitors)
• Protein Kinase Inhibitors (pharmacology)