Ultrastructural localization of α1-syntrophin and neuronal nitric oxide synthase in normal skeletal myofiber, and their relation to each other and to dystrophin

Wakayama, Yoshihiro; Inoue, Masahiko; Murahashi, Makoto; Shibuya, Seiji; Jimi, Takahiro; Kojima, Hiroko; Oniki, Hiroaki

doi:10.1007/s004010050733

Cited by 32 publications

(22 citation statements)

References 41 publications

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“…NO is a very small, freely diffusible, and ubiquitous molecule produced constitutively at high levels in muscle by neuronal nitric oxide synthase (NOS-I) (Nakane et al, 1993;Kobzik et al, 1994;Silvagno et al, 1996). NOS-I is complexed at its N terminus to ␣1-syntrophin, which, in turn, is linked to the dystrophin cytoskeleton, especially in fasttwitch fibers; in dystrophic muscles without dystrophin, NOS-I is reduced and displaced to the cytoplasm (Brenman et al, 1995Chang et al, 1996;Chao et al, 1996;Grozdanovic et al, 1996;Wakayama et al, 1997;Hemler, 1999). NO is also made constitutively by NOS-III and by inducible NOS-II activity and transduces signals in vascular endothelium and smooth muscle, brain, and liver.…”

Section: Introductionmentioning

confidence: 99%

A Role for Nitric Oxide in Muscle Repair: Nitric Oxide–mediated Activation of Muscle Satellite Cells

Anderson

2000

MBoC

383

369

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Muscle satellite cells are quiescent precursors interposed between myofibers and a sheath of external lamina. Although their activation and recruitment to cycle enable muscle repair and adaptation, the activation signal is not known. Evidence is presented that nitric oxide (NO) mediates satellite cell activation, including morphological hypertrophy and decreased adhesion in the fiber-lamina complex. Activation in vivo occurred within 1 min after injury. Cell isolation and histology showed that pharmacological inhibition of nitric oxide synthase (NOS) activity prevented the immediate injury-induced myogenic cell release and delayed the hypertrophy of satellite cells in that muscle. Transient activation of satellite cells in contralateral muscles 10 min later suggested that a circulating factor may interact with NO-mediated signaling. Interestingly, satellite cell activation in muscles of mdx dystrophic mice and NOS-I knockout mice quantitatively resembled NOS-inhibited release of normal cells, in agreement with reports of displaced and reduced NOS expression in dystrophin-deficient mdx muscle and the complete loss of NOS-I expression in knockout mice. Brief NOS inhibition in normal and mdx mice during injury produced subtle alterations in subsequent repair, including apoptosis in myotube nuclei and myotube formation inside laminar sheaths. Longer NOS inhibition delayed and restricted the extent of repair and resulted in fiber branching. A model proposes the hypothesis that NO release mediates satellite cell activation, possibly via shear-induced rapid increases in NOS activity that produce "NO transients." INTRODUCTIONAfter muscle injury, satellite cells are activated and recruited to cycle as precursors for new muscle formation. Between injury and proliferation in vivo, satellite cells express immediate early genes after 3-6 h (Weiss, 1994;Kami et al., 1995) and muscle regulatory genes after 6 h (Grounds et al., 1992) in concert with proliferating cell nuclear antigen (Chambers and McDermott, 1996). The expression of these genes, release of growth factors such as bFGF, and DNA synthesis 24 -30 h later are used to characterize muscle regeneration in injured and dystrophic muscle (Grounds and McGeachie, 1989;Anderson et al., 1995;Floss et al., 1997 Floss et al., , 1998. The timing and sequence of events are specific to those of repair (Megeney et al., 1996;Li et al., 1997;McIntosh et al., 1998) but similar to those of development (Rudnicki and Jaenisch, 1995;Yun and Wold, 1996).The fine structure of satellite cells, positioned intimately between the fiber sarcolemma and the external lamina (Mauro, 1961;Ishikawa, 1966), changes during their transition from quiescence to activation. Nuclei enlarge and become euchromatic. The typical attenuated organelle-poor cytoplasm expands, and organelles such as mitochondria and rough endoplasmic reticulum hypertrophy (Schultz, 1976;Snow, 1977;Schultz et al., 1978Schultz et al., , 1985. However, although activation is recognized as essential to repair and defined as precursor s...

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Section: Introductionmentioning

confidence: 99%

A Role for Nitric Oxide in Muscle Repair: Nitric Oxide–mediated Activation of Muscle Satellite Cells

Anderson

2000

MBoC

383

369

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“…These findings imply that nNOS molecule associates with dystrophin molecule directly or indirectly. Our previous ultrastructural studies confirmed the close association of ␣1-syntrophin and nNOS (Wakayama et al, 1997). Very recently, Kameya et al (1999) generated ␣1-syntrophin knock-out mice that lacked nNOS immunoreactivity in the sarcolemma region of skeletal muscle.…”

Section: Discussionmentioning

confidence: 52%

“…In skeletal muscle, NO acts as a signaling molecule that is released from the dystrophin-glycoprotein complex and is involved in the regulation of myocyte development (Lee et al, 1994;Wang et al, 1995), acetylcholine receptor function at the neuromuscular junction (Wang et al, 1995), and muscle contractility (Kobzik et al, 1994). In skeletal muscle, NO is generated by nNOS, which is found at the myofiber periphery (Frandsen et al, 1996;Grozdanovic et al, 1995;Kobzik et al, 1994) when stained sections of skeletal muscle are examined with the light microscope, and is located close to the cytoplasmic face of the muscle plasma membrane (Wakayama et al, 1997) when studied with the electron microscope.…”

Section: Discussionmentioning

confidence: 98%

Localization of sarcoglycan, neuronal nitric oxide synthase, β‐dystroglycan, and dystrophin molecules in normal skeletal myofiber: Triple immunogold labeling electron microscopy

Wakayama

Inoue

Kojima

et al. 2001

Microscopy Res & Technique

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In order to investigate the mode of existence of the sarcoglycan complex, neuronal nitric oxide synthase (nNOS), beta-dystroglycan, and dystrophin in the normal skeletal myofiber, we examined the ultrastructural localization and mutual spatial relationship of nNOS, beta-dystroglycan, dystrophin, and the individual components of the sarcoglycan complex by using triple immunogold labeling electron microscopy. Each molecule of alpha-, beta-, gamma- and delta-sarcoglycans is located intracellularly or extracellularly near the muscle plasma membrane mostly in accordance with the sarcoglycan antigenic sites against which the antibodies were generated. The association of different two and/or three sarcoglycan molecules out of alpha-, beta-, gamma- and delta-sarcoglycan molecules was frequently observed. Each molecule of nNOS, beta-dystroglycan, and dystrophin was ultrastructurally noted along the cell surface of normal skeletal myofibers. Moreover, the close relation of a sarcoglycan molecule with beta-dystroglycan and dystrophin, and the association of nNOS with dystrophin were also confirmed ultrastructurally. Thus, this study demonstrated that the constituting molecules of the sarcoglycan complex, nNOS, beta-dystroglycan, and dystrophin existed in the form of a cluster at the normal muscle plasma membrane. The association of nNOS with dystrophin and its associated glycoproteins may form a macromolecular signaling complex at the muscle plasma membrane.

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“…This pattern of nNOS distribution is invariably found in skeletal muscles of both myotome and branchial arch origin (Grozdanovic et al, 1995). By electron microscopy, Wakayama et al (1997) have detected nNOS at the inner surface of the sarcolemma, where it clusters in the costameres, as well as in subsarcolemmal areas near mitochondria, which may actually represent caveolae (see below).…”

Section: Nnos Is Lozalized At the Sarcolemma Of Extrafusal And Intrafmentioning

confidence: 94%

NO message from muscle

Grozdanovic

2001

Microscopy Res & Technique

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The synthesis of the free radical gas nitric oxide (NO) is catalyzed by the enzyme NO synthase (NOS). NOS converts arginine and molecular oxygen to NO and citrulline in a reaction that requires NADPH, FAD, FMN, and tetrahydrobiopterin as cofactors. Three types of NOS have been identified by molecular cloning. The activity of the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) is Ca(2+)/calmodulin-dependent, whereas that the inducible NOS (iNOS) is Ca(2+)-insensitive. The predominant NOS isoform in skeletal muscle is nNOS. It is present at the sarcolemma of both extra- and intrafusal muscle fibers. An accentuated accumulation of nNOS is found in the endplate area. This strict sarcolemmal localization of nNOS is due its association with the dystrophin-glycoprotein complex, which is mediated by the syntrophins. The activity of nNOS in skeletal muscle is regulated by developmental, myogenic, and neurogenic influences. NO exerts several distinct effects on various aspects of skeletal muscle function, such as excitation-contraction coupling, mitochondrial energy production, glucose metabolism, and autoregulation of blood flow. Inside the striated muscle fibers, NO interacts directly with several classes of proteins, such as soluble guanylate cyclase, ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, glyceraldehyde-3-phosphate dehydrogenase, and mitochondrial respiratory chain complexes, as well as radical oxygen species. In addition, NO produced and released by contracting muscle fibers diffuses to nearby arterioles where it acts to inhibit reflex sympathetic vasoconstriction.

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Ultrastructural localization of α1-syntrophin and neuronal nitric oxide synthase in normal skeletal myofiber, and their relation to each other and to dystrophin

Cited by 32 publications

References 41 publications

A Role for Nitric Oxide in Muscle Repair: Nitric Oxide–mediated Activation of Muscle Satellite Cells

A Role for Nitric Oxide in Muscle Repair: Nitric Oxide–mediated Activation of Muscle Satellite Cells

Localization of sarcoglycan, neuronal nitric oxide synthase, β‐dystroglycan, and dystrophin molecules in normal skeletal myofiber: Triple immunogold labeling electron microscopy

NO message from muscle

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