Recent evidence has linked mitochondrial dysfunction and DNA damage, increased oxidative stress in skeletal muscle, and insulin resistance (IR). The purpose of this study was to determine the role of the DNA repair enzyme, human 8-oxoguanine DNA glycosylase/apurinic/apyrimidinic lyase (hOGG1), on palmitate-induced mitochondrial dysfunction and IR in primary cultures of skeletal muscle derived from hind limb of ogg1(-/-) knockout mice and transgenic mice, which overexpress human (hOGG1) in mitochondria (transgenic [Tg]/MTS-hOGG1). Following exposure to palmitate, we evaluated mitochondrial DNA (mtDNA) damage, mitochondrial function, production of mitochondrial reactive oxygen species (mtROS), mitochondrial mass, JNK activation, insulin signaling pathways, and glucose uptake. Palmitate-induced mtDNA damage, mtROS, mitochondrial dysfunction, and activation of JNK were all diminished, whereas ATP levels, mitochondrial mass, insulin-stimulated phosphorylation of Akt (Ser 473), and insulin sensitivity were increased in primary myotubes isolated from Tg/MTS-hOGG1 mice compared to myotubes isolated from either knockout or wild-type mice. In addition, both basal and maximal respiratory rates during mitochondrial oxidation on pyruvate showed a variable response, with some animals displaying an increased respiration in muscle fibers isolated from the transgenic mice. Our results support the model that DNA repair enzyme OGG1 plays a pivotal role in repairing mtDNA damage, and consequently, in mtROS production and regulating downstream events leading to IR in skeletal muscle.
Pubmed ID: 23748360 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This unknown targets Mitochondria Complex V (ATP Synthase) alpha subunit
View all literature mentionsThis unknown targets Mitochondria Complex IV (Cytochrome C Oxidase) subunit IV
View all literature mentionsThis monoclonal targets SAPK/JNK (56G8) Rabbit mAb
View all literature mentionsThis polyclonal targets PGC-1 (K-15)
View all literature mentionsThis polyclonal targets Superoxide Dismutase 2
View all literature mentionsThis polyclonal targets Glucose Transporter GLUT4
View all literature mentionsThis polyclonal targets Phospho-IRS-1 (Ser1101)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473) (587F11) Mouse mAb
View all literature mentionsThis monoclonal targets SAPK / JNK, phospho (Thr183 / Tyr185)
View all literature mentionsThis polyclonal targets Actin
View all literature mentionsThis monoclonal targets Bovine Complex I (NADH dehydrogenase), 39 kDa subunit NDUFA9
View all literature mentionsThis monoclonal targets Bovine Complex II, 70 kDa Fp subunit
View all literature mentionsThis monoclonal targets Complex IV (COX), subunit III
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentions