An animal model to evaluate the function and regulation of the adaptively evolving stress protein SEP53 in oesophageal bile damage responses

Squamous epithelium in mammals has evolved an atypical stress response involving down-regulation of the classic HSP70 protein and induction of sets of proteins including one named SEP53. This atypical stress response might be due to the unusual environmental pressures placed on squamous tissue. In fact, SEP53 plays a role as an anti-apoptotic factor in response to DNA damage induced by deoxycholic acid stresses implicated in oesophageal reflux disease. SEP53 also has a genetic signature characteristic of an adaptively and rapidly evolving gene, and this observation has been used to imply a role for SEP53 in immunity. Physiological models of squamous tissue are required to further define the regulation and function of SEP53. We examined whether porcine squamous epithelium would be a good model to study SEP53, since this animal suffers from a bile-reflux disease in squamous oesophageal tissue. We have (1) cloned and sequenced the porcine SEP53 locus from porcine bacterial artificial chromosome genomic DNA, (2) confirmed the strikingly divergent nature of the C-terminal portion of the SEP53 gene amongst mammals, (3) discovered that a function of the conserved N-terminal domain of the gene is to maintain cytoplasmic localisation, and (4) examined SEP53 expression in normal and diseased porcine pars oesophagea. SEP53 expression in porcine tissue was relatively confined to gastric squamous epithelium, consistent with its expression in normal human squamous epithelium. Immunohistochemical staining for SEP53 protein in normal and damaged pars oesophagea demonstrated significant stabilisation of SEP53 protein in the injured tissue. These results suggest that porcine squamous epithelium would be a robust physiological model to examine the evolution and function of the SEP53 stress pathway in modulating stress-induced responses in squamous tissue

Effect of s-methylmethionine sulphonium chloride on oesophagogastric ulcers in pigs

Objective To assess the value of s- methylmethionine sulphonium chloride ( SMMSC) ( 200 mg/ kg) on nutritional performance of pigs and as prevention or therapy for oesophagogastric ulcers. Design Sixty pigs from a high health status herd with continuing oesophagogastric ulcer problems were endoscopically assessed for the presence or absence of oesophagogastric ulcers. Forty- eight pigs were then selected and allocated according to an initial oesophagogastric epithelial ( ulcer score) classification to replicated treatment groups in a 2 x 2 factorial design. Weight gain and feed intake were measured over 49 d, after which pigs were killed and stomachs were collected, re- examined and scored for oesophagogastric ulceration. Results There was no difference over the 49 d in weight gain, feed intake and backfat in pigs with and without SMMSC supplementation between pigs with or without fully developed oesophagogastric ulcers at the start of the study. In pigs with an initially low ulcer score, feeding SMMSC did not prevent further oesophagogastric ulcer development. No significant effect of SMMSC was apparent when final mean oesophagogastric ulcer scores were compared in pigs with existing high ulcer score. However, further analysis of the changes in individual pig oesophagogastric ulcer scores during the experiment showed that the observed reductions in scores of the high ulcer group was significantly different from all other groups. Conclusion This study has indicated that supplementation of pig diets with SMMSC cannot be justified unless the slight ulcer score improvement observed could be translated to some commercial production advantage such as a reduction in pig mortalities due to oesophagogastric ulcers. This study has further confirmed the benefit of endoscopy as a tool to enable objective assessment of oesophageal gastric health