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Tat-CCT2 Protects the Neurons from Ischemic Damage by Reducing Oxidative Stress and Activating Autophagic Removal of Damaged Protein in the Gerbil Hippocampus.
Kwon, Hyun Jung; Jeon, Hong Jun; Choi, Goang-Min; Hwang, In Koo; Kim, Dae Won; Moon, Seung Myung.
Afiliación
  • Kwon HJ; Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea.
  • Jeon HJ; Department of Biomedical Sciences, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
  • Choi GM; Department of Neurosurgery, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, 05355, South Korea.
  • Hwang IK; Department of Thoracic and Cardiovascular Surgery, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon, 24253, South Korea.
  • Kim DW; Department of Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
  • Moon SM; Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea. kimdw@gwnu.ac.kr.
Neurochem Res ; 48(12): 3585-3596, 2023 Dec.
Article en En | MEDLINE | ID: mdl-37561257
CCT2 is a eukaryotic chaperonin TCP-1 ring complex subunit that mediates protein folding, autophagosome incorporation, and protein aggregation. In this study, we investigated the effects of CCT on oxidative and ischemic damage using in vitro and in vivo experimental models. The Tat-CCT2 fusion protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, and the delivered protein was gradually degraded in HT22 cells. Incubation with Tat-CCT2 significantly ameliorated the 200 µM hydrogen peroxide (H2O2)-induced reduction in cell viability in a concentration-dependent manner, and 8 µM Tat-CCT2 treatment significantly alleviated H2O2-induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, CCT2 protein was efficiently delivered into pyramidal cells in CA1 region by intraperitoneally injecting 0.5 mg/kg Tat-CCT2, as opposed to control CCT2. In addition, treatment with 0.2 or 0.5 mg/kg Tat-CCT2 mitigated ischemia-induced hyperlocomotive activity 1 d after ischemia and confirmed the neuroprotective effects by NeuN immunohistochemistry in the hippocampal CA1 region 4 d after ischemia. Tat-CCT2 treatment significantly reduced the ischemia-induced activation of astrocytes and microglia in the hippocampal CA1 region 4 d after ischemia. Furthermore, treatment with 0.2 or 0.5 mg/kg Tat-CCT2 facilitated ischemia-induced autophagic activity and ameliorated ischemia-induced autophagic initiation in the hippocampus 1 d after ischemia based on western blotting for LC3B and Beclin-1, respectively. Levels of p62, an autophagic substrate, significantly increased in the hippocampus following treatment with Tat-CCT2. These results suggested that Tat-CCT2 exerts neuroprotective effects against oxidative stress and ischemic damage by promoting the autophagic removal of damaged proteins or organelles.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Neuroprotectores Límite: Animals Idioma: En Revista: Neurochem Res Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Neuroprotectores Límite: Animals Idioma: En Revista: Neurochem Res Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos