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Altered Expression of Cardiac Ankyrin Repeat Protein and Its Homologue, Ankyrin Repeat Protein with PEST and Proline-Rich Region, in Atrophic Muscles in Amyotrophic Lateral Sclerosis

Nakamura K.a · Nakada C.a · Takeuchi K.d · Osaki M.b · Shomori K.b · Kato S.c · Ohama E.c · Sato K.a · Fukayama M.f · Mori S.e · Ito H.b · Moriyama M.a
aDivision of Molecular Biology, Department of Molecular and Cellular Biology, bDivision of Organ Pathology, Department of Microbiology and Pathology, and cDivision of Neuropathology, Institute of Neurological Science, Tottori University, Yonago, dDepartment of Laboratory Medicine, Research Hospital, and Departments of Pathology, eInstitute of Medical Science, and fGraduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan Pathobiology 2002–03;70:197–203 (DOI:10.1159/000069329)

Abstract

Objectives: Cardiac ankyrin repeat protein, CARP, is a protein that is restrictedly expressed in the heart but barely expressed in skeletal muscles. Since CARP is induced by pressure overload to the heart, it is proposed to be a genetic marker for cardiac hypertrophy. We recently identified a novel protein, ankyrin repeat protein with PEST and proline-rich region (ARPP), which is homologous to CARP and is preferentially expressed in type 1 skeletal muscle fibers (cf. slow fibers). We also found that both ARPP and CARP expression is induced in experimentally denervated skeletal muscles in mice. Based on these findings, we hypothesized that their expression may be induced in skeletal muscles in neurodegenerating disease. This work aimed to determine the expression pattern of ARPP and CARP in amyotrophic lateral sclerosis (ALS). Methods: In this study, we immunohistochemically analyzed the expression of ARPP and CARP in skeletal muscles of 9 ALS cases. Results: We found that CARP was aberrantly expressed in atrophic skeletal muscle fibers in ALS. Although ARPP-positive fibers were randomly scattered in a checkerboard-like pattern in normal skeletal muscle, this pattern was absent in ALS muscles. Furthermore, we also found that ARPP was expressed in fast myosin heavy chain-positive fibers (cf. type 2 fiber). Conclusion: These findings suggest that type-specific expression patterns of ARPP and CARP are altered in skeletal muscles of ALS.

 

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