The differentiation of skeletal myoblasts is characterized by permanent withdrawal from the cell cycle and fusion into multinucleated myotubes. Muscle cell survival is critically dependent on the ability of cells to respond to oxidative stress. Base excision repair (BER) is the main repair mechanism of oxidative DNA damage. In this study, we compared the levels of endogenous oxidative DNA damage and BER capacity of @entity19 proliferating myoblasts and their differentiated counterpart, the myotubes. Changes in the expression of oxidative stress marker genes during differentiation, together with an increase in @entity25469 DNA levels in terminally differentiated cells, suggested that reactive @entity26 species are produced during this process. The repair of @entity44036 , which is exclusively processed by long-patch BER, was impaired in cell extracts from myotubes. The repair of a natural abasic site (a preferred substrate for short-patch BER) also was delayed. The defect in BER of terminally differentiated muscle cells was ascribed to the nearly complete lack of @entity13340 and to the strong down-regulation of @entity8388 with subsequent destabilization of DNA ligase IIIalpha. The attenuation of BER in myotubes was associated with significant accumulation of DNA damage as detected by increased DNA single-strand breaks and phosphorylated @entity2006 nuclear foci upon exposure to @entity273 . We propose that in skeletal muscle exacerbated by free @entity130 , the accumulation of DNA repair intermediates, due to attenuated BER, might contribute to @entity528 as seen in @entity6288 and many @entity121 .

Terminally differentiated muscle cells are defective in base excision DNA repair and hypersensitive to XXXX injury.

@entity25469 :: ('MESH:C024829', 'Chemical') :: ['8-hydroxyguanine'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity6288 :: ('MESH:D055948', 'Disease') :: ['sarcopenia'] @entity273 :: ('MESH:D006861', 'Chemical') :: ['hydrogen peroxide'] @entity8388 :: ('22594(Tax:10090)', 'Gene') :: ['XRCC1'] @entity44036 :: ('MESH:C056405', 'Chemical') :: ['2-deoxyribonolactone'] @entity13340 :: ('16881(Tax:10090)', 'Gene') :: ['DNA ligase I'] @entity528 :: ('MESH:D009410', 'Disease') :: ['myofiber degeneration'] @entity121 :: ('MESH:D009135', 'Disease') :: ['muscle disorders'] @entity2006 :: ('15270(Tax:10090)', 'Gene') :: ['H2AX'] @entity130 :: ('MESH:D014947', 'Disease') :: ['radical injury']
@entity26 :: (MESH:D010100,Chemical) :: ['oxygen']
