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Open AccessArticle

Silencing of PARP2 Blocks Autophagic Degradation

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Institute of Genetics, Biological Research Centre, H-6726 Szeged, Hungary
Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, H-1117 Budapest, Hungary
MTA-DE Lendület Laboratory of Cellular Metabolism, H-4032 Debrecen, Hungary
Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 380;
Received: 20 January 2020 / Revised: 4 February 2020 / Accepted: 4 February 2020 / Published: 7 February 2020
(This article belongs to the Special Issue Molecular Role of PARP in Health and Disease)
Poly(ADP-Ribose) polymerases (PARPs) are enzymes that metabolize NAD+. PARP1 and PARP10 were previously implicated in the regulation of autophagy. Here we showed that cytosolic electron-dense particles appear in the cytoplasm of C2C12 myoblasts in which PARP2 is silenced by shRNA. The cytosolic electron-dense bodies resemble autophagic vesicles and, in line with that, we observed an increased number of LC3-positive and Lysotracker-stained vesicles. Silencing of PARP2 did not influence the maximal number of LC3-positive vesicles seen upon chloroquine treatment or serum starvation, suggesting that the absence of PARP2 inhibits autophagic breakdown. Silencing of PARP2 inhibited the activity of AMP-activated kinase (AMPK) and the mammalian target of rapamycin complex 2 (mTORC2). Treatment of PARP2-silenced C2C12 cells with AICAR, an AMPK activator, nicotinamide-riboside (an NAD+ precursor), or EX-527 (a SIRT1 inhibitor) decreased the number of LC3-positive vesicles cells to similar levels as in control (scPARP2) cells, suggesting that these pathways inhibit autophagic flux upon PARP2 silencing. We observed a similar increase in the number of LC3 vesicles in primary PARP2 knockout murine embryonic fibroblasts. We provided evidence that the enzymatic activity of PARP2 is important in regulating autophagy. Finally, we showed that the silencing of PARP2 induces myoblast differentiation. Taken together, PARP2 is a positive regulator of autophagic breakdown in mammalian transformed cells and its absence blocks the progression of autophagy. View Full-Text
Keywords: PARP2; ARTD2; autophagy; LC3; AMPK; mTOR; PARP; nicotinamide-riboside; SIRT1 PARP2; ARTD2; autophagy; LC3; AMPK; mTOR; PARP; nicotinamide-riboside; SIRT1
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Jankó, L.; Sári, Z.; Kovács, T.; Kis, G.; Szántó, M.; Antal, M.; Juhász, G.; Bai, P. Silencing of PARP2 Blocks Autophagic Degradation. Cells 2020, 9, 380.

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