2020-04-26
Low glutathione and glutathione S-transferase levels in Barrett’s esophagus as compared to normal esophageal epithelium; PY1999; Netherlands;_WJD_2020-0426_V001R01_IR94_RvD20200426_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/10076569
Info cited on 2020-04-26-WD7 (資訊引用於 中華民國109年4月26日) by 湯偉晉 (WeiJin Tang)
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Jpn J Cancer Res. 1999 Jan;90(1):81-5.
Low glutathione and glutathione S-transferase levels in Barrett’s esophagus as compared to normal esophageal epithelium.
van Lieshout EM1, Tiemessen DM, Witteman BJ, Jansen JB, Peters WH.
Author information
1
Department of Gastroenterology and Hepatology, University Hospital St. Radboud, Nijmegen, The Netherlands.
Abstract
Patients with Barrett’s esophagus, wherein squamous epithelium has been replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma as compared to the general population. Glutathione S-transferase (GST), a family of detoxification enzymes consisting of class alpha, mu, pi, and theta isoforms, is involved in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett’s mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98 patients with Barrett’s esophagus were taken from both Barrett’s and adjacent normal squamous epithelium. GST enzyme activity towards 1-chloro-2,4-dinitrobenzene was measured, and GST isoenzyme levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high-performance liquid chromatography after conjugation with monobromobimane. Wilcoxon’s signed rank test and Spearman correlation analyses were used for statistical evaluation. As compared with adjacent normal squamous epithelium, GST enzyme activity in Barrett’s epithelium was reduced by 35%, and GST mu, GST pi and GSH levels were reduced by 24%, 30%, and 63%, respectively. However, the minor GST alpha and GST theta levels were higher in Barrett’s epithelium (by 625% and 33%, respectively). High levels of GSH and GSTs in general are correlated with protection against cellular or cytogenetic damage. The observed reduction in GSTs and GSH in Barrett’s epithelium may therefore contribute to the increased cancer risk in this tissue.
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與普通人群相比，Barrett食管患者的鱗狀上皮已被柱狀上皮所代替，患食管腺癌的風險增加。穀胱甘肽S-轉移酶（GST）是由α，mu，pi和theta亞型組成的排毒酶家族，與致癌物的排毒有關，這些酶的水平低與癌症風險高相關。現在，我們比較了Barrett粘膜與鄰近正常鱗狀上皮的GST酶活性，GST同工酶組成和穀胱甘肽（GSH）含量。取自Barrett食管和鄰近正常鱗狀上皮的98例Barrett食管患者的活檢標本。測量了對1-氯-2,4-二硝基苯的GST酶活性，並在用單克隆抗體免疫檢測後通過western印蹟的光密度分析確定了GST同工酶水平。在與一溴二苯胺偶聯後，通過高效液相色譜法測定總GSH含量。Wilcoxon的符號秩檢驗和Spearman相關分析用於統計評估。與鄰近的正常鱗狀上皮相比，巴雷特上皮中的GST酶活性降低了35％，GST mu，GST pi和GSH含量分別降低了24％，30％和63％。但是，巴雷特上皮中的次要GSTα和GST theta水平較高（分別為625％和33％）。通常，高水平的GSH和GST與防止細胞或細胞遺傳學損害相關。因此，觀察到的Barrett上皮中GST和GSH的減少可能導致該組織中癌症風險的增加。
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[Indexed for MEDLINE] Free PMC Article
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