Conclusion
Our findings confirm that the upregulation of ADAR2 promotes Kv1.1 protein expression, which ultimately reduces neuronal damage in the hippocampus of animals with epilepsy.
Material and methods
A rat epilepsy model was induced in vivo using lithium chloride-pilocarpine. We investigated the effect of ADAR2 on epileptic rats through Western blotting, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and histological analysis. Western blotting was aimed at investigating the effect of overexpression of ADAR2 and Kv1.1-interfering RNA (si-Kv1.1) for neuronal apoptosis.
Methods
A rat epilepsy model was induced in vivo using lithium chloride-pilocarpine. We investigated the effect of ADAR2 on epileptic rats through Western blotting, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and histological analysis. Western blotting was aimed at investigating the effect of overexpression of ADAR2 and Kv1.1-interfering RNA (si-Kv1.1) for neuronal apoptosis.
Objective
Potassium voltage-gated channel sub-family A member 1 (Kv1.1), as a shaker homolog potassium channel, displays a special mechanism for posttranscriptional regulation called RNA editing. Adenosine deaminase acting on RNA 2 (ADAR2) can cause abnormal editing or loss of normal editing, which
Results
The overexpression of ADAR2 in epileptic rats led to the increased mRNA and protein expression of Kv1.1 (P < 0.001) and B-cell leukemia/lymphoma 2 protein (Bcl-2) (P < 0.001), whereas the decreased expressions of Bcl-2-associated X protein and cleaved caspases-3/7 at protein levels (P < 0.0001; P < 0.0001; P < 0.01) detected by Western blotting and qRT-PCR experiments. Hematoxylin and eosin staining and Nissl staining revealed the neuroprotection provided by ADAR2 overexpression. The experiments demonstrated that Kv1.1 was regulated by ADAR2. ADAR2 overexpression increased neuronal survival in in vivo experiments through the elevation of Bcl-2 levels (P < 0.05) and reduction of cleaved caspase-3/7 activity (P < 0.0001; P < 0.01). In the recovery experimental group that involved silencing Kv1.1, the beneficial effects of overexpressing ADAR2 were no longer observed (P < 0.05).