Regulatory mechanisms for senescence marker protein 30 expression

衰老标志蛋白30表达的调控机制

• 批准号: 23500838
• 负责人: ARAI Hideaki
• 金额: $ 2.5万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23500838/
• 关键词: 老化; 加齢; アンチエイジング; 遺伝子; シグナル伝達; FOXO; ストレス耐性; サーチュイン; SMP30; 長寿

Senescence marker protein 30 (SMP30) was identified as a marker protein which shows substantial decrease in ageing rat liver. The molecular mechanisms regulating SMP30 expression is unclear. Elucidation of this regulatory mechanisms is crucial for development of countermeasures against age-related decline of physical fitness and age-associated diseases. Ageing is a highly regulated process with evolutionally conserved signal transduction mechanisms, among which insulin-insulin like growth factor signaling (IIS) is predominantly important. In this study, I found that SMP30 expression in human HepG2 cells was regulated by IIS. Detailed analysis of human SMP30 gene indicated that SMP30 is regulated by Forkhead box transcription factor class O (FoxO), an ortholog of worm longevity gene daf-16. However, direct demonstration of FoxO involvement was hardly feasible because of the extremely low level of SMP30 expression in HepG2, probably reflecting lack of cofactor(s) for FoxO regulation.

衰老标记蛋白 30 (SMP30) 被鉴定为显示衰老大鼠肝脏显着减少的标记蛋白。调节SMP30表达的分子机制尚不清楚。阐明这种调节机制对于制定针对年龄相关体能下降和年龄相关疾病的对策至关重要。衰老是一个高度调控的过程，具有进化上保守的信号转导机制，其中胰岛素-胰岛素样生长因子信号转导（IIS）最为重要。在这项研究中，我发现人HepG2细胞中SMP30的表达受到IIS的调节。对人类 SMP30 基因的详细分析表明，SMP30 受 Forkhead box 转录因子 O 类 (FoxO) 调控，FoxO 是蠕虫长寿基因 daf-16 的直系同源物。然而，直接证明 FoxO 参与几乎不可行，因为 HepG2 中 SMP30 表达水平极低，这可能反映出缺乏 FoxO 调节的辅因子。