| RRC ID |
71925
|
| 著者 |
Oikawa T, Fukuda T, Yamashita T, Tomita H, Ozaki T.
|
| タイトル |
Lentiviral expression of calpain-1 C2-like domain peptide prevents glutamate-induced cell death in mouse hippocampal neuronal HT22 cells.
|
| ジャーナル |
In Vitro Cell Dev Biol Anim
|
| Abstract |
Glutamate neurotoxicity is involved in neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Excess glutamate causes caspase-independent programmed cell death via oxidative stress and calcium influx. Our previous study showed that calpain-1 localizes to both the cytoplasm and mitochondria, where apoptosis-inducing factor (AIF) is cleaved by calpain-1 and translocates to the nucleus to induce DNA fragmentation. The autoinhibitory region of calpain-1 conjugated with the cell-penetrating peptide HIV1-Tat (namely Tat-μCL) specifically prevents the activity of mitochondrial calpain-1 and attenuates neuronal cell death in animal models of retinitis pigmentosa, as well as glutamate-induced cell death in mouse hippocampal HT22 cells. In the present study, we constructed a lentiviral vector expressing the Tat-μCL peptide and evaluated its protective effect against glutamate-induced cell death in HT22 cells. Lentiviral transduction with Tat-μCL significantly suppressed glutamate-induced nuclear translocation of AIF and DNA fragmentation. The findings of the present study suggest that the stable expression of Tat-μCL may be a potential gene therapy modality for neurodegenerative diseases.
|
| 巻・号 |
58(4)
|
| ページ |
289-294
|
| 公開日 |
2022-4-1
|
| DOI |
10.1007/s11626-022-00683-w
|
| PII |
10.1007/s11626-022-00683-w
|
| PMID |
35469046
|
| MeSH |
Animals
Apoptosis Inducing Factor / genetics
Apoptosis Inducing Factor / metabolism
Calpain* / genetics
Calpain* / metabolism
Cell Death
Glutamic Acid* / metabolism
Glutamic Acid* / toxicity
Hippocampus / metabolism
Mice
Oxidative Stress
Peptides / metabolism
|
| IF |
1.665
|
| リソース情報 |
| 遺伝子材料 |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
