Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production

Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such...

Full description

Bibliographic Details
Main Authors: Carnagarin, R., Carlessi, R., Newsholme, P., Dharmarajan, Arunasalam, Dass, C.
Format: Journal Article
Published: Pergamon 2016
Online Access:http://hdl.handle.net/20.500.11937/38035
_version_ 1848755210420224000
author Carnagarin, R.
Carlessi, R.
Newsholme, P.
Dharmarajan, Arunasalam
Dass, C.
author_facet Carnagarin, R.
Carlessi, R.
Newsholme, P.
Dharmarajan, Arunasalam
Dass, C.
author_sort Carnagarin, R.
building Curtin Institutional Repository
collection Online Access
description Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such as obesity, type 2 diabetes, metabolic syndrome and polycystic ovarian syndrome. Chronic inflammation shifts muscle metabolism towards increased glycolysis and decreased oxidative metabolism. In the present study, we demonstrate a novel effect of PEDF on cellular metabolism in mouse cell line (C2C12) and human primary skeletal muscle cells. PEDF addition to skeletal muscle cells induced enhanced phospholipase A2 activity. This was accompanied with increased production of reactive oxygen species in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner that triggered a shift towards a more glycolytic phenotype. Extracellular flux analysis and glucose consumption assays demonstrated that PEDF treatment resulted in enhanced glycolysis but did not change mitochondrial respiration. Our results demonstrate that skeletal muscle cells express a PEDF-inducible oxidant generating system that enhances glycolysis but is sensitive to antioxidants and NADPH oxidase inhibition.
first_indexed 2025-11-14T08:52:41Z
format Journal Article
id curtin-20.500.11937-38035
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T08:52:41Z
publishDate 2016
publisher Pergamon
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-380352017-09-13T14:13:45Z Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production Carnagarin, R. Carlessi, R. Newsholme, P. Dharmarajan, Arunasalam Dass, C. Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such as obesity, type 2 diabetes, metabolic syndrome and polycystic ovarian syndrome. Chronic inflammation shifts muscle metabolism towards increased glycolysis and decreased oxidative metabolism. In the present study, we demonstrate a novel effect of PEDF on cellular metabolism in mouse cell line (C2C12) and human primary skeletal muscle cells. PEDF addition to skeletal muscle cells induced enhanced phospholipase A2 activity. This was accompanied with increased production of reactive oxygen species in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner that triggered a shift towards a more glycolytic phenotype. Extracellular flux analysis and glucose consumption assays demonstrated that PEDF treatment resulted in enhanced glycolysis but did not change mitochondrial respiration. Our results demonstrate that skeletal muscle cells express a PEDF-inducible oxidant generating system that enhances glycolysis but is sensitive to antioxidants and NADPH oxidase inhibition. 2016 Journal Article http://hdl.handle.net/20.500.11937/38035 10.1016/j.biocel.2016.06.013 Pergamon restricted
spellingShingle Carnagarin, R.
Carlessi, R.
Newsholme, P.
Dharmarajan, Arunasalam
Dass, C.
Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
title Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
title_full Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
title_fullStr Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
title_full_unstemmed Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
title_short Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
title_sort pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through nadph oxidase-dependent reactive oxygen species production
url http://hdl.handle.net/20.500.11937/38035