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柯萨奇病毒和腺病毒受体在实验性自身免疫性心肌炎大鼠心脏中的表达

Expression of coxsackievirus and adenovirus receptor in hearts of rats with experimental autoimmune myocarditis.

作者信息

Ito M, Kodama M, Masuko M, Yamaura M, Fuse K, Uesugi Y, Hirono S, Okura Y, Kato K, Hotta Y, Honda T, Kuwano R, Aizawa Y

机构信息

First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan.

出版信息

Circ Res. 2000 Feb 18;86(3):275-80. doi: 10.1161/01.res.86.3.275.

Abstract

The expression of coxsackievirus and adenovirus receptor (CAR) was dominant in the brains and hearts of mice until the newborn phase. There is no detailed information concerning the relation between the expression of CAR and development of hearts. It is also uncertain whether CAR is able to be induced in adult hearts after cardiac injury. We demonstrated that CAR was abundant in the hearts of newborn rats but was barely detectable in the hearts of adult rats. The expression of CAR in rat hearts with experimental autoimmune myocarditis, which was induced by immunization of purified cardiac myosin, was serially investigated. Active myocarditis was observed from day 15 after immunization. By immunohistochemistry, cardiomyocytes were strongly stained for CAR antibody from days 24 to 42. CAR mRNA was also detected from days 18 to 30 by using reverse transcription-polymerase chain reaction. In the next experiment, the induction of CAR on isolated cardiomyocytes was investigated. CAR was barely detectable in cultured cardiomyocytes by Western blot analysis after isolation. This molecule gradually appeared along with the creation of clusters and beating of cardiomyocytes. Furthermore, the induction of CAR in cultured cardiomyocytes increased after supplement with conditioned medium of rat splenocytes activated by concanavalin A. In conclusion, rat CAR is expressed strongly in the hearts of newborn rats and is suppressed in those of adult rats. The expression of CAR is enhanced during the active phase of experimental autoimmune myocarditis and is induced by inflammatory mediators. CAR may play a role in cell-to-cell contact and adhesion of cardiomyocytes.

摘要

柯萨奇病毒和腺病毒受体(CAR)在小鼠的脑和心脏中表达占主导地位,直至新生期。关于CAR表达与心脏发育之间的关系,目前尚无详细信息。心脏损伤后,成年心脏中是否能够诱导CAR表达也不确定。我们证明,CAR在新生大鼠心脏中丰富,但在成年大鼠心脏中几乎检测不到。对通过纯化心肌肌凝蛋白免疫诱导的实验性自身免疫性心肌炎大鼠心脏中CAR的表达进行了系列研究。免疫后第15天观察到活动性心肌炎。通过免疫组织化学,从第24天到第42天,心肌细胞被CAR抗体强烈染色。通过逆转录-聚合酶链反应,在第18天到第30天也检测到了CAR mRNA。在接下来的实验中,研究了分离的心肌细胞上CAR的诱导情况。分离后,通过蛋白质印迹分析在培养的心肌细胞中几乎检测不到CAR。随着心肌细胞聚集的形成和跳动,这种分子逐渐出现。此外,用伴刀豆球蛋白A激活的大鼠脾细胞条件培养基补充后,培养的心肌细胞中CAR的诱导增加。总之,大鼠CAR在新生大鼠心脏中强烈表达,在成年大鼠心脏中受到抑制。CAR的表达在实验性自身免疫性心肌炎的活动期增强,并由炎症介质诱导。CAR可能在心肌细胞的细胞间接触和黏附中发挥作用。

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