2026-03-06T02:46:56Z https://iwate-u.repo.nii.ac.jp/oai

oai:iwate-u.repo.nii.ac.jp:00015784 2023-05-15T12:51:15Z 1515:1519

Calpain-1 C2L domain peptide protects mouse hippocampus-derived neuronal HT22 cells against glutamate-induced oxytosis SUGAWARA, Mayu ABE, Takumi KASAI, Shuya ITOH, Ken OZAKI, Taku Mitochondrial calpain-1 Oxytosis Cell penetrating peptide Hippocampal HT22 cells Neurodegeneration Calpains are Ca2+-dependent cysteine proteases; their aberrant activation is associated with several neurodegenerative diseases. The μ-calpain catalytic subunit, calpain-1, is located in the cytoplasm as well as in the mitochondria. Mitochondrial calpain-1 cleaves apoptosis-inducing factor (AIF), leading to apoptotic cell death. We have previously reported that short peptides of calpain-1 C2-like domain conjugated with cell penetrating peptide HIV-Tat (Tat-μCL) selectively inhibit mitochondrial calpain-1 and effectively prevent neurodegenerative diseases of the eye. In this study, we determined whether mitochondrial calpain-1 mediates oxytosis (oxidative glutamate toxicity) in hippocampal HT22 cells using Tat-μCL and newly generated polyhistidine-conjugated μCL peptide and compared their efficacies in preventing oxytosis. TUNEL assay and single strand DNA staining revealed that both μCL peptides inhibited glutamate-induced oxytosis. Additionally, both the peptides suppressed the mitochondrial AIF translocation into the nucleus. All polyhistidine-μCL peptides (containing 4–16 histidine residues) showed higher cell permeability than Tat-μCL. Notably, tetrahistidine (H4)-μCL exerted the highest cytoprotective activity. Thus, H4-μCL may be a potential peptide drug for calpain-1-mediated neurodegenerative diseases such as Alzheimer's disease. journal article Elsevier B.V. 2021-08-12 VoR application/pdf Biochemistry and Biophysics Reports 27 101101 24055808 https://iwate-u.repo.nii.ac.jp/record/15784/files/bbr-v27p101101.pdf https://iwate-u.repo.nii.ac.jp/records/15784 eng info:doi/10.1016/j.bbrep.2021.101101 © 2021 The Authors. https://creativecommons.org/licenses/by-nc-nd/4.0/