1. Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis
- Author
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Harjit Pal Bhattoa, Ibolya Horváth, Beáta Bódi, András Vida, László Vígh, Péter Bai, Zsolt Török, Mária Péter, Laura Jankó, Dóra Bojcsuk, Judit Márton, Magdolna Szántó, Karen Uray, Zoltán Papp, Imre Gombos, Gábor Balogh, and Balint L. Balint
- Subjects
Male ,0301 basic medicine ,Poly ADP ribose polymerase ,Cell Line ,Cell membrane ,Gene Knockout Techniques ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Homeostasis ,Muscle, Skeletal ,Molecular Biology ,Chemistry ,Cholesterol ,Cell Membrane ,Skeletal muscle ,Dihydrotestosterone ,Lipid metabolism ,Cell Biology ,Lipidome ,Lipid Metabolism ,Sterol ,Rats ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Sterol Regulatory Element Binding Protein 1 ,Poly(ADP-ribose) Polymerases ,030217 neurology & neurosurgery - 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.
- Published
- 2018