Ontogenetic and phylogenetic mechanisms involved in the loss of proliferation activity in mammalian cardiomyocytes after birth.

个体发生和系统发生机制涉及哺乳动物心肌细胞出生后增殖活性的丧失。

• 批准号: 24650245
• 负责人: KAWAHARA Koichi
• 金额: $ 2.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24650245/
• 关键词: 心筋細胞増殖; イモリ心筋; ラット心筋; 正帰還制御ループ; 心筋損傷後再生; 心筋細胞増殖能喪失

Shortly after birth, mammalian cardiomyocytes irreversibly exit from the cell cycle and become terminally differentiated. In contrast, a newt’s heart can be completely repaired and the organ’s function can be completely restored following damage. The genetic cues for the irreversible exit from the cell cycle in mammalian cardiomyocytes soon after birth remain largely unknown. This study aims at elucidating ontogenetic and phylogenetic mechanisms involved in the loss of proliferation activity in mammalian cardiomyocytes soon after birth. To investigate the causes underling the lack of proliferation activity in mammalian cardiomyocytes, I examined the effect of an extract derived from newt regenerating hearts on terminally differentiated rat cardiomyocytes. This study has demonstrated that the exposure of rat cardiomyocytes to the protein extract derived from newt regenerating hearts resulted in an increase in the proliferation activity of rat cardiomyocytes, suggesting that the unknown protein(s) involved in the newt extract possibly opened a positive-feedback loop of ROS-p38 MAPK-Cx43 contributing to the loss of proliferation activity in mammalian cardiomyocytes.

出生后不久，哺乳动物心肌细胞不可逆地退出细胞周期，并成为终末分化。相比之下，蝾螈的心脏可以完全修复，器官的功能可以在损伤后完全恢复。哺乳动物心肌细胞在出生后不久就不可逆转地退出细胞周期的遗传线索在很大程度上仍然未知。本研究旨在阐明哺乳动物出生后不久心肌细胞增殖活性丧失的个体发生和系统发育机制。为了研究哺乳动物心肌细胞缺乏增殖活性的原因，我研究了蝾螈再生心脏提取物对终末分化大鼠心肌细胞的影响。本研究表明，将大鼠心肌细胞暴露于蝾螈再生心脏的蛋白质提取物导致大鼠心肌细胞增殖活性增加，表明蝾螈提取物中涉及的未知蛋白质可能打开了ROS-p38 MAPK-Cx43的正反馈回路，导致哺乳动物心肌细胞增殖活性丧失。

项目成果

北海道大学・大学院情報科学研究科・細胞情報工学研究室

北海道大学信息科学研究生院细胞信息工学研究室

Negaitive-feedback regulation of ATP release during ischemia in cardiac myocytes

心肌细胞缺血期间 ATP 释放的负反馈调节

• 发表时间: 2012
• 作者: Kawahara;K. Kunugi;S;Matsuyama;D. and Iwabuchi;S.
• 通讯作者: S.

Negaitive-feedback regulation of ATP release during ischemia in cardiac myocytes. In: Proceedings of the IFMBE 39, Long

心肌细胞缺血期间 ATP 释放的负反馈调节。

• 发表时间: 2012
• 作者: Kawahara;K. Kunugi;S;Matsuyama;D. and Iwabuchi;S.
• 通讯作者: S.

Spatio-temporal spread of neuronal death after focal photolysis of caged glutamate in neuron/astrocyte co-cultures.

神经元/星形胶质细胞共培养物中笼中谷氨酸的局部光解后神经元死亡的时空扩散。

• DOI: 10.1016/j.neuint.2013.03.010
• 发表时间: 2013
• 期刊: Neurochemistry International
• 影响因子: 4.2
• 作者: Sadahiro Iwabuchi

Negative-feedback regulation of ATP release during ischemia in cardiac myocytes.

心肌细胞缺血期间 ATP 释放的负反馈调节。

• 发表时间: 2012
• 期刊: IFMBE Proceedings
• 作者: Koichi Kawahara