Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study is the first to examine site-specific changes in mucosal antioxidants and expression and localization of heat shock proteins (HSPs) following the induction of subacute esophagitis and after recovery using an established animal model. Distal, middle, and proximal samples were excised from anesthetized opossums 24 hr after three consecutive days of 45-min perfusion with saline or 100 mmol/liter HCI, or seven days after acid in recovery animals. Compared to controls, acid-induced erosive esophagitis significantly increased glutathione peroxidase and HSP90 at all sites and HSP60 proximally. Reduced glutathione was significantly decreased distally, as was HSP72 at distal and middle sites. No changes in superoxide dismutase or catalase occurred. After recovery, superoxide dismutase, catalase, and HSP expression were not different from controls. Glutathione peroxidase and glutathione were significantly decreased distally. Similar differential stress responses may occur in patients with chronic gastroesophageal reflux and could be important in the pathogenesis of reflux esophagitis.
 ...
PMID:Analysis of mucosal stress response in acid-induced esophagitis in opossum. 1218 45

Chronic gastroesophageal reflux disease is a known risk factor for Barrett's esophagus (BE), which induces oxidative mucosal damage. Glutathione peroxidase-3 (GPx3) is a secretory protein with potent extracellular antioxidant activity. In this study, we have investigated the mRNA and protein expression of GPx3, and explored promoter hypermethylation as an epigenetic mechanism for GPx3 gene inactivation during Barrett's carcinogenesis. Quantitative real-time reverse transcription polymerase chain reaction on 42 Barrett's adenocarcinomas (BAs) revealed consistently reduced levels of GPx3 mRNA in 91% of tumor samples. GPx3 promoter hypermethylation was detected in 62% of Barrett's metaplasia, 82% of dysplasia, and 88% of BA samples. Hypermethylation of both alleles of GPx3 was most frequently seen in BAs (P = .001). Immunohistochemical staining of GPx3 in matching tissue sections (normal, BE, Barrett's dysplasia, and BA) revealed strong immunostaining for GPx3 in normal esophageal and gastric tissues. However, weak to absent GPx3 staining was observed in Barrett's dysplasia and adenocarcinoma samples where the promoter was hypermethylated. The degree of loss of immunohistochemistry correlated with the hypermethylation pattern (monoallelic versus biallelic). The observed high frequency of promoter hypermethylation and progressive loss of GPx3 expression in BA and its associated lesions, together with its known function as a potent antioxidant, suggest that epigenetic inactivation and regulation of glutathione pathway may be critical in the development and progression of BE.
 ...
PMID:Hypermethylation and loss of expression of glutathione peroxidase-3 in Barrett's tumorigenesis. 1622 8