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Sarco(endo)plasmic reticulum ca2+ATPases (SERCA1 and 2) 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.
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2003 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, no 12, 5057-5062 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To investigate the composition of the fibers in human extraocular muscles (EOMs) with respect to the sarco(endo)plasmic reticulum Ca(2+)ATPases (SERCA)-1 and -2 and to investigate possible correlations between SERCA and myosin heavy chain (MyHC) composition. METHODS: EOM samples were processed for immunocytochemistry with monoclonal antibodies specific against SERCA1 (fast isoform), SERCA2 (slow isoform), or different MyHCs. A total of 1571 fibers were analyzed. Microsomal EOM fractions were analyzed with SDS-PAGE and immunoblots. RESULTS: The fast fibers, containing MyHCIIa, accounted for 79% of the fibers in the orbital layer (OL) and 74% in the global layer (GL). More than 99% of these fibers contained SERCA1, and 86% of them coexpressed SERCA1 and -2. Almost all slow fibers stained with SERCA2; 54% of those in the GL and all in the OL coexpressed SERCA1 and -2. Fifteen percent of the fibers in the GL and less than 1% in the OL were MyHCeom(pos)/MyHCIIa(neg) fibers. All these contained SERCA1 and in the OL also stained strongly with anti-SERCA2. Biochemically SERCA2 was more abundant than SERCA1. CONCLUSIONS: The human EOMs had a very complex pattern of expression of the major protein regulating fiber relaxation rate. The coexistence of SERCA1 and -2, together with complex mixtures of MyHCs in most of the fibers provide the human EOMs with a unique molecular portfolio that allows a highly specific fine-tuning regimen of contraction and relaxation.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology , 2003. Vol. 44, no 12, 5057-5062 p.
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:umu:diva-3936DOI: 10.1167/iovs.03-0218PubMedID: 14638697OAI: oai:DiVA.org:umu-3936DiVA: diva2:142850
Available from: 2004-05-05 Created: 2004-05-05 Last updated: 2017-12-14Bibliographically 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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 890
Keyword
Ophtalmology, extraocular, muscle, myosin, protein c, laminin, serca, immunocytochemistry, human, Oftalmiatrik
National Category
Ophthalmology
Research subject
Ophtalmology
Identifiers
urn:nbn:se:umu:diva-260 (URN)91-7305-638-3 (ISBN)
Public defence
2004-05-28, E04, 6E, Norrlands Universitetssjukhus, Umeå, 13:15
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Available from: 2004-05-05 Created: 2004-05-05 Last updated: 2011-04-08Bibliographically approved

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