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HDL promotes adiponectin gene expression via the CAMKK/CAMKIV pathway
https://kagawa-u.repo.nii.ac.jp/records/9561
https://kagawa-u.repo.nii.ac.jp/records/956148eb8b15-0732-479c-9e2e-3bae949b793e
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本文 (602.9 kB)
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内容の要旨 (70.1 kB)
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審査の結果の要旨 (85.6 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2022-04-22 | |||||||||||
| タイトル | ||||||||||||
| タイトル | HDL promotes adiponectin gene expression via the CAMKK/CAMKIV pathway | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| その他（別言語等）のタイトル | ||||||||||||
| その他のタイトル | HDL(高比重リポタンパク質)は、CaMKK/CaMKⅣ pathwayを介してアディポネクチンの遺伝子発現を促進する | |||||||||||
| 言語 | ja | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
小林, 俊博
× 小林, 俊博
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Adiponectin (APN) is an adipokine that protects against diabetes and atherosclerosis. High-density lipoprotein (HDL) mediates reverse cholesterol transport, which also protects against atherosclerosis. In this process, the human homolog of the B class type I scavenger receptor (SR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. The level of circulating APN is positively correlated with the serum level of HDL-cholesterol. In this study, we investigated whether HDL stimulates the gene expression of APN through the Ca2+/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) cascade. APN expression was examined using real-time PCR and western blot analysis in 3T3-L1 cells incubated with HDL. CaMKIV activity was assessed by the detection of activation loop phosphorylation (at Thr196 residue), and the effect of the constitutively active form, CaMKIVc, on APN promoter activity was investigated. Our results showed that HDL stimulated APN gene expression via hSR-BI/CLA-1. Furthermore, we explored the signaling pathways by which HDL stimulated APN expression in 3T3-L1 cells. The stimulation of APN gene expression by HDL appears to be mediated by CaMKK, as STO-609, a specific inhibitor of CaMKK2, prevents this effect. We revealed that CaMKIVc increased APN gene transcriptional activity, and the CaMKIV-dominant negative mutant blocked the effect of HDL on APN promoter activity. Finally, knockdown of hSR-BI/CLA-1 also canceled the effect of HDL on APN gene expression. These results suggest that HDL has an important role to improve the function of adipocytes by activating hSR-BI/CLA-1, and CaMKK/CaMKIV pathway is conceivable as one of the signaling pathways of this activation mechanism. | |||||||||||
| 言語 | en | |||||||||||
| 学位名 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位授与機関 | ||||||||||||
| 識別子Scheme | kakenhi | |||||||||||
| 識別子 | 16201 | |||||||||||
| 言語 | ja | |||||||||||
| 機関名 | 香川大学 | |||||||||||
| 言語 | en | |||||||||||
| 機関名 | Kagawa University | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2022-03-24 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第809号 | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | Copyright: © Society for Endocrinology 2022 | |||||||||||
| PubMed番号 | ||||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 34845988 | |||||||||||
| 関連サイト | ||||||||||||
| 関連タイプ | isVersionOf | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1530/jme-20-0211 | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | P | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | adiponectin | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | HDL | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | SR-BI | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | CaMKK/CaMKIV pathway | |||||||||||
