Lentiviral expression of calpain-1 C2-like domain peptide prevents glutamate-induced cell death in mouse hippocampal neuronal HT22 cells.

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Publisher: Springer
Document Type: Report; Brief article
Length: 226 words

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Keywords: Mitochondrial calpain-1; Hippocampal HT22 cells; Apoptosis-inducing factor (AIF); Neurodegeneration; Lentiviral expression 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. Author Affiliation: (1) Department of Biological Chemistry, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, 020-8550, Morioka, Iwate, Japan (2) Department of Biological Science, Graduate School of Science and Engineering, Iwate University, 4-3-5 Ueda, 020-8551, Morioka, Iwate, Japan (e) tozaki@iwate-u.ac.jp Article History: Registration Date: 04/06/2022 Received Date: 12/07/2021 Accepted Date: 03/30/2022 Online Date: 04/25/2022 Byline:

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Gale Document Number: GALE|A702795694