title: Changes in skeletal muscle expression of AQP1 and AQP4 in dystrophinopathy and dysferlinopathy patients.
abstract: Transmembrane water transport is mediated by aquaporins (AQPs), of which AQP1 and AQP4 are expressed in skeletal muscle. AQP4 expression is reduced in Duchenne muscular dystrophy (DMD) patients, and is reported to correlate with decreased alpha1-syntrophin and altered osmotic permeability. In this study, we assessed the relationship between AQP1, AQP4, dystrophin and alpha1-syntrophin in dystrophinopathy and dysferlinopathy patients. Muscle biopsies of patients with DMD (n = 8) and limb-girdle muscular dystrophy type 2B (LGMD2B; n = 5) were screened for AQP1 and AQP4 expression by real-time quantitative RT-PCR or Western blot and immunohistochemistry. AQP expression was further analyzed in primary myotubes derived from DMD and LGMD2B patients by cell culture and immunohistochemistry. AQP1 transcript and protein expression was significantly elevated in DMD biopsies, and was localized to the sarcolemma of muscle fibers and endothelia of muscle capillaries. AQP4 was significantly reduced despite normal dystrophin and alpha1-syntrophin in dysferlinopathy patients, while expression of AQP1 was variably upregulated. Expression of AQP1 and AQP4 was normal in patient-derived primary myotubes, suggesting that altered AQPs observed in biopsies are likely secondary to the dystrophic process. Our study shows that AQP4 downregulation can occur in muscular dystrophies with either normal or disrupted expression of dystrophin-associated proteins, and that this might be associated with upregulation of AQP1.
authors.affiliation: Kids Heart Research, The Children's Hospital at Westmead, Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Locked Bag 4001, Westmead, Sydney, NSW, 2145, Australia.
authors.forename: Carol G
authors.initials: CG
authors.lastname: Au
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Butler
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Egan
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Cooper
authors.forename: Harriet P
authors.initials: HP
authors.lastname: Lo
authors.forename: Alison G
authors.initials: AG
authors.lastname: Compton
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.forename: David S
authors.initials: DS
authors.lastname: Winlaw
mesh_terms: D000293:Adolescent; D000328:Adult; D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C496020:AQP1 protein, human; C496030:AQP4 protein, human; D051401:Aquaporin 4; D002135:Calcium-Binding Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D009124:Muscle Proteins; C091825:syntrophin alpha1; D051398:Aquaporin 1