Reduced expression of Ca^(2+)-regulating proteins in the upper gastrointestinal tract of patients with achalasia  

作　　者：Harald Fischer Judith Fischer Peter Boknik Ulrich Gergs Wilhelm Schmitz Wolfram Domschke Jan W Konturek Joachim Neumann 

机构地区：[1]Medizinische Klinik und Poliklinik B, Universittsklinikum Mnster, 48129 Mnster, Germany [2]Institut fr Pharmakologie und Toxikologie, Universittsklinikum Mnster, 48149 Mnster, Germany [3]Institut fr Pharmakologie und Toxikologie, Martin-Luther-Universitt Halle-Wittenberg, 06112 Halle (Saale), Germany [4]Klinik fr Innere Medizin/Gastroenterologie, Elbe Klinikum Stade, 21682 Stade, Germany

出　　处：《World Journal of Gastroenterology》2006年第37期6002-6007,共6页世界胃肠病学杂志（英文版）

基　　金：Supported by grants from the "Deutsche Forschungsgemeinschaft" (DFG) and the Interdisciplinary Center of Clinical Research (IZKF) Mnster

摘　　要：AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ 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 profi les 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 signif icantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus mightbe of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.AIM： 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）. CONCLUSION： 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＋.

关 键 词：Esophageal and gastric motility ESOPHAGUS CALSEQUESTRIN CALRETICULIN 

分 类 号：R57[医药卫生—消化系统]