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N-型糖鎖変調はNav1.5心筋型Na+チャネルの発現を制御しゲーティング機構を調節する
http://hdl.handle.net/10559/16859
http://hdl.handle.net/10559/1685910750811-31c2-40ae-906e-478c8ff66129
| Item type | デフォルトアイテムタイプ（フル）(1) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2021-08-09 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Disruption of asparagine-linked glycosylation to rescue and alter gating of the Nav1.5-Na+ channel | |||||||||||
| 言語 | en | |||||||||||
| タイトル | ||||||||||||
| タイトル | N-型糖鎖変調はNav1.5心筋型Na+チャネルの発現を制御しゲーティング機構を調節する | |||||||||||
| 言語 | ja | |||||||||||
| 作成者 |
王, 普
× 王, 普
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| アクセス権 | ||||||||||||
| アクセス権 | metadata only access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述 | SCN5A gene encodes the voltage-gated sodium channel NaV1.5 which is composed of a pore-forming α subunit of the channel. Asparagine (N)-linked glycosylation is one of the common post-translational modifications in proteins. The aim of this study was to investigate impact of N-linked glycosylation disruption on the Na+ channel, and the mechanism by which glycosylation regulates the current density and gating properties of the Na+ channel. The NaV1.5-Na+ channel isoform (α submit) derived from human was stably expressed in human embryonic kidney (HEK)-293 cells (Nav1.5-HEK cell). We applied the whole-cell patch-clamp technique to study the impact of N-linked glycosylation disruption in Nav1.5-HEK cell. Inhibition of the N-glycosylation with tunicamycin caused a significant increase of NaV1.5 channel current (INa) when applied for 24 h. Tunicamycin shifted the steady-state inactivation curve to the hyperpolarization direction, whereas the activation curve was unaffected. Recovery from inactivation was prolonged, while the fast phase (τfast) and the slow phase (τslow) of the current decay was unaffected by tunicamycin. INa was unaffected by tunicamycin in the present of a proteasome inhibitor MG132 [N-[(phenylmethoxy)carbonyl]-L-leucy-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide], while it was significantly increased by tunicamycin in the presence of a lysosome inhibitor butyl methacrylate (BMA). These findings suggest that N-glycosylation disruption rescues the NaV1.5 channel possibly through the alteration of ubiquitin-proteasome activity, and changes gating properties of the NaV1.5 channel by modulating glycan milieu of the channel protein. | |||||||||||
| 言語 | en | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 大分大学 | |||||||||||
| 言語 | ja | |||||||||||
| 日付 | ||||||||||||
| 日付 | 2021-01-01 | |||||||||||
| 日付タイプ | Issued | |||||||||||
| 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 | |||||||||||
| 識別子 | ||||||||||||
| 識別子 | http://hdl.handle.net/10559/16859 | |||||||||||
| 識別子タイプ | HDL | |||||||||||
| 関連情報 | ||||||||||||
| 関連タイプ | isVersionOf | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1007/s00380-020-01736-4 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第657号 | |||||||||||
| 学位名 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2021-03-25 | |||||||||||
| 学位授与機関 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位授与機関名 | 大分大学 | |||||||||||
