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Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Uppsala University.
University of Bonn.
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2006 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 47, no 10, 4188-4193 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To examine the distribution of myosin-binding protein C (MyBP-C) in human extraocular muscles (EOMs) and to correlate the myosin heavy chain (MyHC) and the MyBP-C composition of the fibers. METHODS: Samples from 17 EOMs, 3 levator palpebrae (LP), and 6 limb muscles were analyzed with SDS-PAGE and immunoblot or processed for immunocytochemistry with monoclonal antibodies (mAbs) against MyBP-C-fast, MyBP-C-slow, MyHCIIa, MyHCI, MyHCsto, MyHCalpha-cardiac, and MyHCemb. RESULTS: In the limb muscle samples, fast fibers were labeled with anti-MyBP-C-fast and anti-MyBP-C-slow, whereas the slow fibers were immunostained with anti-MyBP-C-slow only, in accordance with previous studies. In 11 EOM samples MyBP-C-fast was not detected, and weak staining with anti-MyBP-C-fast was seen only in a few fibers in the proximal part of 2 muscles. The mAb against MyBP-C-slow labeled all fibers, but fibers containing MyHCI were generally more strongly stained. In the levator palpebrae, immunostaining with anti-MyBP-C-fast was present in some fibers labeled with anti-MyHCIIa and/or anti-MyHCeom. MyBP-C-fast and -intermediate were not detected biochemically in the EOMs. CONCLUSIONS: The lack of MyBP-C-fast and intermediate is an additional feature of the human EOM allotype. The true EOMs have a unique myofibrillar protein isoform composition reflecting their special structural and functional properties. The levator palpebrae muscle phenotype is intermediate between that of the EOMs and the limb muscles.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology , 2006. Vol. 47, no 10, 4188-4193 p.
Keyword [en]
Adolescent, Adult, Aged; 80 and over, Antibodies; Monoclonal, Carrier Proteins/*metabolism, Electrophoresis; Polyacrylamide Gel, Female, Humans, Immunoblotting, Immunohistochemistry, Male, Muscle; Skeletal/metabolism, Myosin Heavy Chains/*metabolism, Myosins/metabolism, Oculomotor Muscles/*metabolism, Protein Isoforms
National Category
URN: urn:nbn:se:umu:diva-12672DOI: 10.1167/iovs.05-1496PubMedID: 17003405OAI: diva2:152343
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2013-12-12Bibliographically approved
In thesis
1. Human extraocular muscles: molecular diversity of a unique muscle allotype
Open this publication in new window or tab >>Human extraocular muscles: molecular diversity of a unique muscle allotype
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: The extraocular muscles (EOMs) are considered a separate class of skeletal muscle, allotype. Myosin is the major contractile protein in muscle. The myosin heavy chain (MyHC) isoforms are the best molecular markers of functional heterogeneity of muscle fibers. The relaxation rate, reflects the rate at which Ca2+ is transported back into the sarcoplasmic reticulum (SR) mostly by SR Ca2+ATPase (SERCA). Myosin binding protein C (MyBP-C), plays a physiological role in regulating contraction. The laminins (Ln) are the major non-collagenous components of the basement membrane (BM) surrounding muscle fibers and are important for muscle fiber integrity.

Methods: Adult human EOMs were studied with SDS-PAGE, immunoblots and immunocytochemistry, the latter with antibodies against six MyHC, 2 SERCA, 2 MyBP-C and 8 laminin chain isoforms. The capillary density was also determined.

Results: Most fibers contained a mixture of MyHC isoforms. Three major groups of fibers could be distinguished. Fast fibers that stained with anti-MyHCIIa, slow fibers that stained with anti-MyHCI and MyHCeompos/MyHCIIaneg-fibers that stained with neither of these antibodies but with anti-MyHCI+IIa+eom and anti-MyHCeom. A majority of the fibers contained both SERCA1 and 2 whereas 1% were unstained with both antibodies. Biochemically SERCA2 was more abundant than SERCA1. MyBP-Cfast was not present in the EOMs and MyBP-Cslow was only detected immunocytochemically. The extrasynaptical BM of the EOM muscle fibers contained Lna2, b1, b2, g1, a4 and a5 chains. The capillary density in the EOMs was very high (1050 +/-190 capillaries/mm2) and significantly (p<0.05) higher in the orbital than in the global layer.

Conclusions: The co-existence of complex mixtures of several crucial protein isoforms provide the human EOMs with a unique molecular portfolio that a) allows a highly specific fine-tuning regime of contraction and relaxation, and b) imparts structural properties that are likely to contribute to protection against certain neuromuscular diseases.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2004. 51 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 890
Ophtalmology, extraocular, muscle, myosin, protein c, laminin, serca, immunocytochemistry, human, Oftalmiatrik
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Research subject
urn:nbn:se:umu:diva-260 (URN)91-7305-638-3 (ISBN)
Public defence
2004-05-28, E04, 6E, Norrlands Universitetssjukhus, Umeå, 13:15
Available from: 2004-05-05 Created: 2004-05-05 Last updated: 2011-04-08Bibliographically approved

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