Cyclooxygenase-1 and an alternatively spliced mRNA in the rat stomach: effects of aging and ulcers

Abstract

Prostaglandins play a critical role in gastric mucosal cytoprotection and decrease progressively with age. Cyclooxygenase (COX), the rate-limiting enzyme for prostaglandin synthesis, exists in two isoforms, COX-1 and COX-2. The rat COX-1 gene expresses an alternatively spliced mRNA COX-1 splice variant (SV) that may, at best, code for a truncated COX-1 protein. With the use of competitive PCR, we determined whether COX gene expression was altered in the stomach with increasing age and after gastric ulcer induction. COX-1 mRNA was significantly reduced in the aged, and COX-1SV mRNA was significantly higher in the adults compared with the young and aged stomach. Levels of COX-1 and COX-2 were similarly expressed in the normal stomach. In acute gastric ulcers, only COX-2 mRNA levels were significantly elevated. When ulcers were undergoing healing and repair, COX-1 and COX-2 mRNA levels were significantly elevated. Age-related changes in COX-1 and COX-1SV but not COX-2 mRNA may alter gastric mucosal cytoprotection. Furthermore, COX-1 and COX-2 may both contribute to the healing of a gastric ulcer.

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

“…Because this transcript lacks exon 1, which contains the initiating codon for translation, it has been considered to encode a nonsense COX protein (Kitzler et al, 1995). Interestingly, however, studies of the rat gastrointestinal tract show differential expression of this variant relative to COX-1 in aging stomach (Vogiagis et al, 2000). Moreover, expression of this variant was elevated in colorectal tumors, and its expression was reduced following treatment with NSAIDs (Vogiagis et al, 2001).…”

Polyphenol metabolites from colonic microbiota exert anti‐inflammatory activity on different inflammation models

“…Primer sequences for TNF-a and IFN-c were from Bradesi et al [23]. b-Actin and IL1-b were from Tsune et al [24] COX-1 was from Vogiagis et al [25] and IL-8 from Kim et al [26].…”

Acetaminophen and the Cyclooxygenase-3 Puzzle: Sorting out Facts, Fictions, and Uncertainties

“…A splice variant of COX-1 lacking exon 9 was reported in human fibroblasts (Diaz et al, 1992), and recently it was shown that the mRNA transcript for this COX-1 variant is present in various human tissues; however, the corresponding protein is either not formed or subject to rapid proteolytic degradation (Schneider et al, 2005). Yet another COX-1 splice variant containing an intronic sequence was described in rat tracheal epithelial cells (Kitzler et al, 1995), rat stomach (Vogiagis et al, 2000), and rat colorectal tumors (Vogiagis et al, 2001). Another COX-1 splice variant was shown to be present in endothelial cells (Hla, 1996).…”