Comprehensive assessment of chamber-specific and transmural heterogeneity in myofilament protein phosphorylation by top-down mass spectrometry

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GREGORİCH Z. R., Peng Y., Lane N. M., WOLFF J. J., Wang S., Guo W., ...Daha Fazla

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, cilt.87, ss.102-112, 2015 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 87
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.yjmcc.2015.08.007
  • Dergi Adı: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.102-112
  • Anahtar Kelimeler: Transmural heterogeneity, Chamber heterogeneity, Phosphorylation, Mass spectrometry, Myofilament, CARDIAC TROPONIN-I, HUMAN HEART-FAILURE, MYOCARDIAL-INFARCTION, VENTRICULAR MYOCYTES, ALPHA-MYOSIN, PROTEOMICS, TROPOMYOSIN, CONTRACTILE, HYPERTROPHY, RELAXATION
  • Abdullah Gül Üniversitesi Adresli: Hayır

Özet

The heart is characterized by a remarkable degree of heterogeneity, the basis of which is a subject of active investigation. Myofilament protein post-translational modifications (PTMs) represent a critical mechanism regulating cardiac contractility, and emerging evidence shows that pathological cardiac conditions induce contractile heterogeneity that correlates with transmural variations in the modification status of myofilament proteins. Nevertheless, whether there exists basal heterogeneity in myofilament protein PTMs in the heart remains unclear. Here we have systematically assessed chamber-specific and transmural variations in myofilament protein PTMs, specifically, the phosphorylation of cardiac troponin I (cTnI), cardiac troponinT (cTnT), tropomyosin (Tpm), and myosin light chain 2 (MLC2). We show that the phosphorylation of cTnI and cam vary in the different chambers of the heart, whereas the phosphorylation of MLC2 and cTnT does not. In contrast, no significant transmural differences were observed in the phosphorylation of any of the myofilament proteins analyzed. These results highlight the importance of appropriate tissue sampling-particularly for studies aimed at elucidating disease mechanisms and biomarker discovery-in order to minimize potential variations arising from basal heterogeneity in myofilament PTMs in the heart. (C) 2015 Elsevier Ltd. All rights reserved.