000			03073na a2200265 4500
999			_c9263 _d9263
003			H12O
005			20210625062809.0
008			130622s2012 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91007 _aArenas Barbero, Joaquín _eInstituto de Investigación
100			_aGarcía-Consuegra Galiana, Inés _91867 _eInstituto de Investigación i+12
100			_9345 _aMartín Casanueva, Miguel Ángel _eBioquímica Clínica
100			_aRubio, Juan C. _92181 _eInstituto de Investigación i+12
245	0	2	_aA Transcriptomic Approach to Search for Novel Phenotypic Regulators in McArdle Disease, _h[artículo]
260			_bPlos One, _c2012
300			_a7(2):e31718.
500			_aFormato Vancouver: Nogales-Gadea G, Consuegra-García I, Rubio JC, Arenas J, Cuadros M, Camara Y et al. A transcriptomic approach to search for novel phenotypic regulators in McArdle disease. PLoS One. 2012;7(2):e31718.
501			_aPMID: 22347505
504			_aContiene 36 referencias
520			_aMcArdle disease is caused by lack of glycogen phosphorylase (GP) activity in skeletal muscle. Patients experience exercise intolerance, presenting as early fatigue and contractures. In this study, we investigated the effects produced by a lack of GP on several genes and proteins of skeletal muscle in McArdle patients. Muscle tissue of 35 patients and 7 healthy controls were used to identify abnormalities in the patients' transcriptomic profile using low-density arrays. Gene expression was analyzed for the influence of variables such as sex and clinical severity. Differences in protein expression were studied by immunoblotting and 2D electrophoresis analysis, and protein complexes were examined by two-dimensional, blue native gel electrophoresis (BN-PAGE). A number of genes including those encoding acetyl-coA carboxylase beta, m-cadherin, calpain III, creatine kinase, glycogen synthase (GS), and sarcoplasmic reticulum calcium ATPase 1 (SERCA1), were found to be downregulated in patients. Specifically, compared to controls, GS and SERCA1 proteins were reduced by 50% and 75% respectively; also, unphosphorylated GS and SERCA1 were highly downregulated. On BN-PAGE analysis, GP was present with GS in two muscle protein complexes. Our findings revealed some issues that could be important in understanding the physiological consequences of McArdle disease: (i) SERCA1 downregulation in patients could result in impaired calcium transport in type II (fast-twitch) muscle fibers, leading to early fatigability during exercise tasks involving type II fibers (which mostly use glycolytic metabolism), i. e. isometric exercise, lifting weights or intense dynamic exercise (stair climbing, bicycling, walking at a very brisk pace), (ii) GP and GS were found together in two protein complexes, which suggests a new regulatory mechanism in the activity of these glycogen enzymes.
710			_9625 _aInstituto de Investigación imas12
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276513/ _yAcceso libre
942			_n0 _2ddc _cART