期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1863, 期 11, 页码 1399-1412出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2018.07.013
关键词
Androgen; Cholesterol; PARP; Skeletal muscle; Dihydrotestosterone
资金
- NKFIH [K123975, PD121138, K120669, PROJEKT2017-44, GINOP-2.3.2-15-2016-00006, EFOP-3.6.3-VEKOP-16-2017-00009, EFOP-3.6.2-16-2017-00006]
- Bolyai fellowship of the Hungarian Academy of Sciences
- New National Excellence Program grant of the Ministry of Human Capacities [UNKP-17-3-IV-DE-96]
- MOLMEDEX FUN-OMICS [GINOP-2.3.3-15-2016-00007]
- Debrecen Venture Catapult Program [EFOP-3.6.1-16-2016-00022]
- European Social Fund
- European Regional Development Fund
There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of PARP2 induced characteristic changes in the lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle. Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone, an anabolic steroid. Thus, skeletal muscle fibers in PARP2(-/-) mice were stronger compared to those of their wild-type littermates. In addition, we detected changes in the dynamics of the cell membrane, suggesting that lipidome changes also affect the biophysical characteristics of the cell membrane. In in silico and wet chemistry studies, we identified lipid species that can decrease the expression of PARP2 and potentially phenocopy the genetic abruption of PARP2, including artificial steroids. In view of these observations, we propose a new role for PARP2 as a lipid-modulated regulator of lipid metabolism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据