title: Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy.
abstract: Duchenne muscular dystrophy is caused by dystrophin mutations that lead to structural instability of the sarcolemma membrane, myofiber degeneration/regeneration and progressive muscle wasting. Here we show that myogenic Akt signaling in mouse models of dystrophy promotes increased expression of utrophin, which replaces the function of dystrophin thereby preventing sarcolemma damage and muscle wasting. In contrast to previous suggestions that increased Akt in dystrophy was a secondary consequence of pathology, our findings demonstrate a pivotal role for this signaling pathway such that modulation of Akt can significantly affect disease outcome by amplification of existing, physiological compensatory mechanisms.
authors.affiliation: Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Angela K
authors.initials: AK
authors.lastname: Peter
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Ko
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Kim
authors.forename: Nigel
authors.initials: N
authors.lastname: Hsu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Suhn
authors.initials: S
authors.lastname: Rhie
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Ling
authors.initials: L
authors.lastname: Zeng
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Rachelle H
authors.initials: RH
authors.lastname: Crosbie
mesh_terms: D000818:Animals; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012508:Sarcolemma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D049411:Utrophin / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D049411:Utrophin; D051057:Proto-Oncogene Proteins c-akt