title: Fibre-related nitric oxide synthase (NOS) in Duchenne muscular dystrophy.
abstract: Nitric oxide (NO) mediates fundamental physiological actions on skeletal muscle. The loss of NO synthase (NOS) from the sarcolemma was assumed to be associated with development of Duchenne muscular dystrophy (DMD). We have, however, recently reported that, in contrast to the commonly accepted view, NOS expression in DMD myofibres is up-regulated. This poses the question of the fibre type-specific NOS expression in DMD muscles and how the NOS expression is related to the regeneration or degeneration status. To address this issue, we examined localization of NOS isoforms I, II and III in skeletal muscles of DMD patients employing immunohistochemical labelling with tyramide signal amplification complemented with enzyme histochemistry. We found that NOS immunolabelling as well as metabolic enzyme activity in DMD muscles were heterogeneously distributed along the fibre length of DMD muscle fibres revealing regenerating and degenerate (hypercontracted) fibres as well as normal segments. Like in normal muscles, positive NOS immunoreactivity was found to be associated with fast-oxidative glycolytic (FOG) phenotype. The regeneration status of NOS-positive segments was deduced from the presence of neonatal and developmental myosin heavy chains. High NOS expression in regenerating DMD muscle fibres can be well reconciled with reports about the protective role of endogenous NO in inflammatory diseases and in muscle repair.
authors.affiliation: Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103 Leipzig, Germany. punktk@medizin.uni-leipzig.de
authors.forename: K
authors.initials: K
authors.lastname: Punkt
authors.forename: S
authors.initials: S
authors.lastname: Schering
authors.forename: M
authors.initials: M
authors.lastname: Fritzsche
authors.forename: G
authors.initials: G
authors.lastname: Asmussen
authors.forename: E A
authors.initials: EA
authors.lastname: Minin
authors.forename: V E
authors.initials: VE
authors.lastname: Samoilova
authors.forename: F-U
authors.initials: FU
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Schmitz
authors.forename: M
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: W
authors.initials: W
authors.lastname: Paulus
authors.forename: U
authors.initials: U
authors.lastname: Müller-Werdan
authors.forename: J
authors.initials: J
authors.lastname: Slezak
authors.forename: G
authors.initials: G
authors.lastname: Koehler
authors.forename: W
authors.initials: W
authors.lastname: Boecker
authors.forename: I B
authors.initials: IB
authors.lastname: Buchwalow
mesh_terms: D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000201:enzymology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology
chemical_list: D007527:Isoenzymes; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018995:Myosin Heavy Chains