固有的硫化生产对于饮食限制的好处至关重要
Christopher Hine1, Eylul Harputlugil1, Yue Zhang1
1Department of Genetics and Complex Diseases, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 28, 2014
概括
饮食限制通过转硫化途径 (TSP) 增加硫化 (H2S) 产量,增强抗压能力和寿命. 这种保存机制具有广泛的临床影响.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 老年学是指老年学的学科.
背景情况:
- 饮食限制 (DR) 提供了长寿和抗压力等健康益处,但潜在的机制尚不清楚.
- 硫氨基酸 (SAA) 是参与代谢调节和应激反应的关键营养素.
研究的目的:
- 调查硫氨基酸 (SAA) 和硫化 (H2S) 在调解饮食限制 (DR) 的好处方面的作用.
- 探索转硫途径 (TSP) 在DR介导的寿命和抗压力中的进化保护.
主要方法:
- 利用DR的小鼠模型来研究SAA限制对转硫路径 (TSP) 和H2S生产的影响.
- 研究了SAA补充剂,mTORC1激活和CGL抑制对DR介导的抗压力的影响.
- 使用线粒体蛋白SQR进行了体外研究,并在各种模型生物 (酵母,虫,果,动物) 中检查了TSP依赖的H2S生产.
主要成果:
- SAA的限制上调了氨酸γ-酶 (CGL),增加了H2S的产生,并提供了对肝缺血再输伤害的保护.
- 通过减少H2S水平,SAA补充,mtORC1激活或CGL抑制取消了DR介导的应激抵抗.
- 对TSP依赖的H2S生产在多种物种中得到保护,并与DR介导的寿命有关.
结论:
- 转硫化途径 (TSP) 介导的硫化 (H2S) 生产是一种维持机制,是饮食限制 (DR) 益处的基础.
- 这一途径赋予抗压力和长寿,表明在代谢和与衰老相关的疾病中具有临床翻译的潜力.
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