論文 - 詳細
| RRC ID | 65005 |
|---|---|
| 著者 | Kitagishi H, Minegishi S, Yumura A, Negi S, Taketani S, Amagase Y, Mizukawa Y, Urushidani T, Sugiura Y, Kano K. |
| タイトル | Feedback Response to Selective Depletion of Endogenous Carbon Monoxide in the Blood. |
| ジャーナル | J Am Chem Soc |
| Abstract |
The physiological roles of endogenous carbon monoxide (CO) have not been fully understood because of the difficulty in preparing a loss-of-function phenotype of this molecule. Here, we have utilized in vivo CO receptors, hemoCDs, which are the supramolecular 1:1 inclusion complexes of meso-tetrakis(4-sulfonatophenyl)porphinatoiron(II) with per-O-methylated β-cyclodextrin dimers. Three types of hemoCDs (hemoCD1, hemoCD2, and hemoCD3) that exhibit different CO-affinities have been tested as CO-depleting agents in vivo. Intraperitoneally administered hemoCD bound endogenous CO within the murine circulation, and was excreted in the urine along with CO in an affinity-dependent manner. The sufficient administration of hemoCD that has higher CO-affinity than hemoglobin (Hb) produced a pseudoknockdown state of CO in the mouse in which heme oxygenase-1 (HO-1) was markedly induced in the liver, causing the acceleration of endogenous CO production to maintain constant CO-Hb levels in the blood. The contents of free hemin and bilirubin in the blood plasma of the treated mice significantly increased upon removal of endogenous CO by hemoCD. Thus, a homeostatic feedback model for the CO/HO-1 system was proposed as follows: HemoCD primarily removes CO from cell-free CO-Hb. The resulting oxy-Hb is quickly oxidized to met-Hb by oxidant(s) such as hydrogen peroxide in the blood plasma. The met-Hb readily releases free hemin that directly induces HO-1 in the liver, which metabolizes the hemin into iron, biliverdin, and CO. The newly produced CO binds to ferrous Hb to form CO-Hb as an oxidation-resistant state. Overall, the present system revealed the regulatory role of CO for maintaining the ferrous/ferric balance of Hb in the blood. |
| 巻・号 | 138(16) |
| ページ | 5417-25 |
| 公開日 | 2016-4-27 |
| DOI | 10.1021/jacs.6b02211 |
| PMID | 27057920 |
| MeSH | Animals Carbon Monoxide / blood* Coordination Complexes / pharmacokinetics* Feedback, Physiological Gene Expression Regulation, Enzymologic Heme Oxygenase-1 / genetics Heme Oxygenase-1 / metabolism* Hep G2 Cells Humans Iron / chemistry* Male Membrane Proteins / genetics Membrane Proteins / metabolism* Mice, Inbred C57BL |
| IF | 14.612 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1886) |