000			nam a22 7a 4500
999			_c17087 _d17087
003			PC17087
005			20221124113031.0
008			221124b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91460 _aGarcía Ruiz, Inmaculada _eInstituto de Investigación i+12
100			_91461 _aMuñoz Yagüe, María Teresa _eAparato Digestivo
100			_9514 _aSolís Herruzo, José Antonio _eAparato Digestivo
245	0	0	_aIn vitro treatment of HepG2 cells with saturated fatty acids reproduces mitochondrial dysfunction found in nonalcoholic steatohepatitis. _h[artículo]
260			_bDisease models & mechanisms, _c2015
300			_a8(2):183-91.
500			_aFormato Vancouver: García Ruiz I, Solís Muñoz P, Fernández Moreira D, Muñoz Yagüe T, Solís Herruzo JA. In vitro treatment of HepG2 cells with saturated fatty acids reproduces mitochondrial dysfunction found in nonalcoholic steatohepatitis. Dis Model Mech. 2015 Feb;8(2):183-91.
501			_aPMID: 25540128 PMC4314783
504			_aContiene 47 referencias
520			_aActivity of the oxidative phosphorylation system (OXPHOS) is decreased in humans and mice with nonalcoholic steatohepatitis. Nitro-oxidative stress seems to be involved in its pathogenesis. The aim of this study was to determine whether fatty acids are implicated in the pathogenesis of this mitochondrial defect. In HepG2 cells, we analyzed the effect of saturated (palmitic and stearic acids) and monounsaturated (oleic acid) fatty acids on: OXPHOS activity; levels of protein expression of OXPHOS complexes and their subunits; gene expression and half-life of OXPHOS complexes; nitro-oxidative stress; and NADPH oxidase gene expression and activity. We also studied the effects of inhibiting or silencing NADPH oxidase on the palmitic-acid-induced nitro-oxidative stress and subsequent OXPHOS inhibition. Exposure of cultured HepG2 cells to saturated fatty acids resulted in a significant decrease in the OXPHOS activity. This effect was prevented in the presence of a mimic of manganese superoxide dismutase. Palmitic acid reduced the amount of both fully-assembled OXPHOS complexes and of complex subunits. This reduction was due mainly to an accelerated degradation of these subunits, which was associated with a 3-tyrosine nitration of mitochondrial proteins. Pretreatment of cells with uric acid, an antiperoxynitrite agent, prevented protein degradation induced by palmitic acid. A reduced gene expression also contributed to decrease mitochondrial DNA (mtDNA)-encoded subunits. Saturated fatty acids induced oxidative stress and caused mtDNA oxidative damage. This effect was prevented by inhibiting NADPH oxidase. These acids activated NADPH oxidase gene expression and increased NADPH oxidase activity. Silencing this oxidase abrogated totally the inhibitory effect of palmitic acid on OXPHOS complex activity. We conclude that saturated fatty acids caused nitro-oxidative stress, reduced OXPHOS complex half-life and activity, and decreased gene expression of mtDNA-encoded subunits. These effects were mediated by activation of NADPH oxidase. That is, these acids reproduced mitochondrial dysfunction found in humans and animals with nonalcoholic steatohepatitis.
710			_9273 _aServicio de Medicina del Aparato Digestivo
710			_9625 _aInstituto de Investigación imas12
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314783/ _yAcceso libre
942			_2ddc _cART _n0