Altered expression of the Ca(2+)-binding protein S100A1 in human cardiomyopathy.
The Ca(2+)-binding protein S100A1 displays a tissue-specific expression pattern with highest levels in myocardium and has been shown to interact with SR-proteins regulating the Ca(2+)-induced Ca(2+)-release. We, therefore, hypothesized that changes in S100A1 gene expression might correlate with the pathognomonic finding of altered SR Ca(2+)-transients in human end stage heart failure. To test this hypothesis, we established a specific and sensitive method to analyse S100A1 expression in cardiac tissues by employing hydrophobic interaction-chromatography and reversed-phase high performance liquid chromatography (RP-HPLC) coupled with Electron-Ionisation-Mass-Spectrometry (ESI-MS). Porcine myocardium showed a differential expression of S100A1 with relative protein concentrations of 62 +/- 8% in the right ventricle (RV), 57 +/- 9% in the right atrium (RA), and 25 +/- 15% in the left atrium (LA) as compared to the left ventricle (LV) (100 +/- 10%; P < 0.001). Northern blot analyses confirmed a likewise distribution of porcine S100A1 mRNA implying a regulation on the transcriptional level. Analyses of left ventricular specimen of patients with end stage heart failure (CHF, n = 6; CHD, n = 6) revealed significantly reduced S100A1 protein levels, while integration of S100A1 peaks after RP-HPLC yielded two groups of patients with < 76% (69 +/- 7%, n = 6) and < 35% (23 +/- 12%, n = 6) respectively as compared to controls (100 +/- 8%, n = 3). These data demonstrate for the first time that S100A1 is differentially expressed in myocardium and that in human cardiomyopathy a reduced expression of S100A1 may contribute to a compromised contractility.
Abteilung für Klinische Chemie, Kinderspital, Universität Zürich, Switzerland.
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D000818:Animals; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D002147:Calmodulin / Q000032:analysis; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000737:chemistry; D006352:Heart Ventricles / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D009418:S100 Proteins; D012685:Sepharose / Q000031:analogs & derivatives; D013552:Swine
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D012333:RNA, Messenger; D009418:S100 Proteins; C110294:S100A1 protein; C027176:octyl-sepharose CL-4B; D012685:Sepharose