Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis

Márton, Judit and Péter, Mária and Balogh, Gábor and Bódi, Beáta and Vida, András and Szántó, Magdolna and Bojcsuk, Dora and Jankó, Laura and Bhattoa Harjit, Pál and Gombos, Imre and Uray, Karen and Horváth, Ibolya and Török, Zsolt and Bálint, Bálint László and Papp, Zoltán and Vigh, László and Bay, Péter (2018) Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1863 (11). pp. 1399-1412. ISSN 1388-1981


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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.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 31 Jan 2019 18:38
Last Modified: 31 Jan 2019 18:38

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