| RRC ID |
53915
|
| 著者 |
Márton J, Péter M, Balogh G, Bódi B, Vida A, Szántó M, Bojcsuk D, Jankó L, Bhattoa HP, Gombos I, Uray K, Horváth I, Török Z, Balint BL, Papp Z, Vígh L, Bai P.
|
| タイトル |
Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis.
|
| ジャーナル |
Biochim Biophys Acta Mol Cell Biol Lipids
|
| Abstract |
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.
|
| 巻・号 |
1863(11)
|
| ページ |
1399-1412
|
| 公開日 |
2018-11-1
|
| DOI |
10.1016/j.bbalip.2018.07.013
|
| PII |
S1388-1981(18)30187-2
|
| PMID |
30077797
|
| MeSH |
Animals
Cell Line
Cell Membrane / metabolism
Cholesterol / metabolism*
Dihydrotestosterone / metabolism
Gene Knockout Techniques*
Homeostasis
Lipid Metabolism
Male
Mice
Muscle, Skeletal / metabolism*
Poly(ADP-ribose) Polymerases / genetics*
Poly(ADP-ribose) Polymerases / metabolism
Rats
Sterol Regulatory Element Binding Protein 1 / genetics
|
| IF |
4.402
|
| 引用数 |
3
|
| リソース情報 |
| 遺伝子材料 |
pKM2L-phSREBP2 (RDB05498) |
