Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η
Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the <i>C</i>-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function o...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1827 |
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| author | Hyun Jung Kwon Duk-Soo Kim Woosuk Kim Hyo Young Jung Yeon Hee Yu Young In Ju Dae-Kyoon Park In Koo Hwang Dae Won Kim Dae Young Yoo |
| author_facet | Hyun Jung Kwon Duk-Soo Kim Woosuk Kim Hyo Young Jung Yeon Hee Yu Young In Ju Dae-Kyoon Park In Koo Hwang Dae Won Kim Dae Young Yoo |
| author_sort | Hyun Jung Kwon |
| collection | DOAJ |
| description | Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the <i>C</i>-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H<sub>2</sub>O<sub>2</sub>-induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H<sub>2</sub>O<sub>2</sub> treatment in HT22 cells. Ischemia–reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus. |
| first_indexed | 2024-03-10T18:00:35Z |
| format | Article |
| id | doaj.art-fe1e234677bc454aae2600f1abf23759 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:00:35Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fe1e234677bc454aae2600f1abf237592023-11-20T08:56:18ZengMDPI AGCells2073-44092020-08-0198182710.3390/cells9081827Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3ηHyun Jung Kwon0Duk-Soo Kim1Woosuk Kim2Hyo Young Jung3Yeon Hee Yu4Young In Ju5Dae-Kyoon Park6In Koo Hwang7Dae Won Kim8Dae Young Yoo9Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, KoreaDepartment of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31151, KoreaDepartment of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, KoreaDepartment of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31151, KoreaDepartment of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31151, KoreaDepartment of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31151, KoreaDepartment of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, KoreaDepartment of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, KoreaDepartment of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31151, KoreaCannabinoid receptor-interacting protein 1a (CRIP1a) binds to the <i>C</i>-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H<sub>2</sub>O<sub>2</sub>-induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H<sub>2</sub>O<sub>2</sub> treatment in HT22 cells. Ischemia–reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus.https://www.mdpi.com/2073-4409/9/8/1827cannabinoid receptor–interacting protein 1aoxidative stressischemia14-3-3η |
| spellingShingle | Hyun Jung Kwon Duk-Soo Kim Woosuk Kim Hyo Young Jung Yeon Hee Yu Young In Ju Dae-Kyoon Park In Koo Hwang Dae Won Kim Dae Young Yoo Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η Cells cannabinoid receptor–interacting protein 1a oxidative stress ischemia 14-3-3η |
| title | Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η |
| title_full | Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η |
| title_fullStr | Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η |
| title_full_unstemmed | Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η |
| title_short | Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η |
| title_sort | tat cannabinoid receptor interacting protein reduces ischemia induced neuronal damage and its possible relationship with 14 3 3η |
| topic | cannabinoid receptor–interacting protein 1a oxidative stress ischemia 14-3-3η |
| url | https://www.mdpi.com/2073-4409/9/8/1827 |
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