Different desmin peptides are distinctly deposited in cytoplasmic aggregations and cytoplasm of desmin-related cardiomyopathy patients.
Desmin-related cardiomyopathy is a heterogeneous group of myofibrillar myopathies characterized by aggregates of desmin and related proteins in myocytes. It has been debated how the expression and protein structure are altered in the aggregates and other parts of myocytes in patients. To address this question, we investigated the proteome quantification as well as localization in formalin-fixed and paraffin-embedded specimens of the heart of patients by imaging mass spectrometry and liquid chromatography-mass spectrometry analyses. Fifteen tryptic peptide signals were enriched in the desmin-related cardiomyopathy myocardium, twelve of which were identified as desmin peptides with 14.3- to 27.3-fold increase compared to normal hearts. High-intensity signals at m/z 1032.5 and 1002.5, which were desmin peptides 59-70 at the head portion and 213-222 at the 1B domain, were with infrequent colocalization distributed not only in desmin-positive intracytoplasmic aggregates but also in histologically normal cytoplasm, indicating that desmin protein is fragmented and different types of naturally-occurring truncated proteins ectopically assemble throughout the heart of patients. Thus, in addition to conventional histological identification of protein aggregates, specific desmin peptides show a marked difference in quantity and localization in a tissue section of desmin-related cardiomyopathy and differentiate from other cardiomyopathies. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yukako
Y
Shintani-Domoto
Laboratory for Advanced Lipid Analysis, Health Innovation & Technology Center, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan; Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takahiro
T
Hayasaka
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cellular and Organ Pathology, Akita University, Akita, Japan.
Daichi
D
Maeda
Department of Medical Spectroscopy, Institute for Medical Photonics Research, Preeminent Medical Photonics Education &Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Noritaka
N
Masaki
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan; International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takashi K
TK
Ito
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kei
K
Sakuma
Department of Pathology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan.
Michio
M
Tanaka
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan; International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Katsuya
K
Kabashima
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan; International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Shiro
S
Takei
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan; International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan; Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan; Riken Center for Molecular Imaging Science, Kobe, Japan; Department of Anatomy, The University of Hong Kong, Hong Kong, China; Division of Neural Systematics, National Institute for Physiological Sciences, Okazaki, Japan. Electronic address: setou@hama-med.ac.jp.
Mitsutoshi
M
Setou
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: mfukayama-tky@umin.net.
Masashi
M
Fukayama
D000328:Adult; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology*; D002853:Chromatography, Liquid / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism*; D003893:Desmin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D066329:Protein Aggregates / Q000502:physiology*; D020543:Proteome / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D055815:Young Adult
D003893:Desmin; D010455:Peptides; D066329:Protein Aggregates; D020543:Proteome
Cardiomyopathy; Desmin protein; Imaging mass; Pathology; Spectrometry