Reduced expression of Ca2+-regulating proteins in the upper gastrointestinal tract of patients with achalasia.
OBJECTIVE
To compare expression of Ca(2+)-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia.


METHODS
Sarcoplasmic reticulum Ca(2+) ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profiles of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed.


RESULTS
SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were significantly reduced in patients with achalasia (P < 0.05).


CONCLUSIONS
PLB in the human esophagus might be of lesser importance for regulation of SERCA than in heart. Lower expression of Ca(2+) storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca(2+).
Fischer
Harald
H
Medizinische Klinik und Poliklinik B, Universitätsklinikum Münster, Germany.
Fischer
Judith
J
Boknik
Peter
P
Gergs
Ulrich
U
Schmitz
Wilhelm
W
Domschke
Wolfram
W
Konturek
Jan W
JW
Neumann
Joachim
J
D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D002155:Calsequestrin / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D004931:Esophageal Achalasia / Q000378:metabolism* / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002155:Calsequestrin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C506948:Atp2a2 protein, rat