- 著者
- 中川 靖章 錦見 俊雄 桑原 宏一郎 岡 昌吾 木下 秀之 中尾 一泰 趙 晃済 稲住 英明 加藤 貴雄 中尾 一和 木村 剛 Nishida Motohiro Kato Takao Fukushima Hiroyuki Yamashita Jun K. Wijnen Wino J. Creemers Esther E. Kangawa Kenji Minamino Naoto Nakao Kazuwa Kimura Takeshi
- 出版者
- Wiley Blackwell
- 雑誌
- Journal of the American Heart Association (ISSN:20479980)
- 巻号頁・発行日
- vol.6, no.2, 2017-02
Background-Recent studies have shown that plasma levels of the biologically inactive prohormone for brain natriuretic peptide (proBNP) are increased in patients with heart failure. This can contribute to a reduction in the effectiveness of circulating BNP and exacerbate heart failure progression. The precise mechanisms governing the increase in proBNP remain unclear, however. Methods and Results-We used our recently developed, highly sensitive human proBNP assay system to investigate the mechanisms underlying the increase in plasma proBNP levels. We divided 53 consecutive patients hospitalized with heart failure into 2 groups based on their aortic plasma levels of immunoreactive BNP. Patients with higher levels exhibited more severe heart failure, a higher proportion of proBNP among the immunoreactive BNP forms secreted from failing hearts, and a weaker effect of BNP as estimated from the ratio of plasma cyclic guanosine monophosphate levels to log-transformed plasma BNP levels. Glycosylation at threonines 48 and 71 of human proBNP contributed to the increased secretion of proBNP by attenuating its processing, and GalNAc-transferase (GALNT) 1 and 2 mediated the glycosylation-regulated increase in cardiac human proBNP secretion. Cardiac GALNT1 and 2 expression was suppressed by microRNA (miR)-30, which is abundantly expressed in the myocardium of healthy hearts, but is suppressed in failing hearts. Conclusions-We have elucidated a novel miR-30-GALNT1/2 axis whose dysregulation increases the proportion of inactive proBNP secreted by the heart and impairs the compensatory actions of BNP during the progression of heart failure.
1 0 0 0 OA 神経活動制御におけるHNK-1を中心としたN型糖鎖機能の解析
近年、脳の高次機能に糖鎖が深く関わることが次々に示され、神経系における糖鎖研究の重要性が増している。本研究では神経可塑性の調節に重要な役割を持つHNK-1糖鎖、およびシナプス可塑性調節に中心的な役割を担うAMPA受容体に発現するN型糖鎖を中心に解析を行った。その結果、AMPA受容体上のN型糖鎖が、その細胞表面発現量、細胞表面上での側方拡散の調節などに関わることを明らかにした。また、ペリニューロナルネット上に存在する新規HNK-1糖鎖を同定し、神経可塑性調節に重要なコンドロイチン硫酸鎖の合成を制御していることを明らかにした。