title: Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy.
abstract: BACKGROUND
  Previous studies provide considerable evidence that excitation-contraction coupling may be disturbed at the level of the sarcoplasmic reticulum (SR) in the failing human heart. Disturbed SR function may result from altered expression of calcium-handling proteins.
  
  
  RESULTS
  Levels of SR proteins involved in calcium release (ryanodine receptor), calcium binding (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban) were measured by Western blot analysis in nonfailing human myocardium (n = 7) and in end-stage failing myocardium due to dilated cardiomyopathy (n = 14). The levels of the ryanodine receptor, calsequestrin, and calreticulin were not significantly different in nonfailing and failing human myocardium. Phospholamban protein levels (pentameric form) normalized per total protein were decreased by 18% in the failing myocardium (P < .05). However, phospholamban protein levels were not significantly different in failing and nonfailing myocardium when normalization was performed per calsequestrin. Protein levels of SR calcium ATPase, normalized per total protein or per calsequestrin, were decreased by 41% (P < .001) or 33% (P < .05), respectively, in the failing myocardium. Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by 37% (P < .05) and relative to phospholamban by 28% (P < .05).
  
  
  CONCLUSIONS
  Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medizinische Klinik II und III, Universität Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Meyer
authors.forename: W
authors.initials: W
authors.lastname: Schillinger
authors.forename: B
authors.initials: B
authors.lastname: Pieske
authors.forename: C
authors.initials: C
authors.lastname: Holubarsch
authors.forename: C
authors.initials: C
authors.lastname: Heilmann
authors.forename: H
authors.initials: H
authors.lastname: Posival
authors.forename: G
authors.initials: G
authors.lastname: Kuwajima
authors.forename: K
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: H
authors.initials: H
authors.lastname: Just
authors.forename: G
authors.initials: G
authors.lastname: Hasenfuss
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002155:Calsequestrin / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D000099211:Phospholamban
chemical_list: D000251:Adenosine Triphosphatases; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002148:Calmodulin-Binding Proteins; D037282:Calreticulin; D002155:Calsequestrin; D009124:Muscle Proteins; D012261:Ribonucleoproteins; D019837:Ryanodine Receptor Calcium Release Channel; D000099211:Phospholamban