Intron 1 retaining cyclooxygenase 1 splice variant is induced by osmotic stress in human intestinal epithelial cells
The biological roles of intron 1 retaining cyclooxygenase (Cox) 1 splice variants Cox-3 and PCox-1a (Cox-1ir) are not known. In humans, Cox-3 transcription has previously been shown to occur in the brain and in the aorta. However, conclusive evidence regarding the existence of a human Cox-3 protein...
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Published in | Prostaglandins, leukotrienes and essential fatty acids Vol. 73; no. 5; pp. 343 - 350 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Kidlington
Elsevier Ltd
01.11.2005
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | The biological roles of intron 1 retaining cyclooxygenase (Cox) 1 splice variants Cox-3 and PCox-1a (Cox-1ir) are not known. In humans, Cox-3 transcription has previously been shown to occur in the brain and in the aorta. However, conclusive evidence regarding the existence of a human Cox-3 protein is lacking. We studied the expression of intron 1 retaining cyclooxygenase 1 splice variants in the human colon cancer cell line Caco-2 and in human colonic tissue samples. In Caco-2 cells, their transcription was induced up to 47-fold by osmotic stress. The corresponding protein, however, could not be detected by Western blotting. In human colonic tissue samples derived from intact and inflamed areas, a low level of Cox-1ir mRNA (1500±1280 copies per 100
ng total RNA; mean±standard deviation;
n
=
20
) was also found. In Caco-2 cells, induction of Cox-1ir under osmotic stress was reversed by addition of the organic osmolyte betaine. Under hypertonic but not under isotonic conditions, splice variant-specific degradation of Cox-1ir mRNA using RNA interference resulted in increased production of fully spliced Cox-1 and Cox-2 mRNA (
P
=
0.002
). In summary, our results indicate that the intron 1 retaining Cox-1 splice variant RNA molecules are expressed by human intestinal epithelial cells in a controlled manner, are most likely not translated and play a regulatory role in the cyclooxygenase mediated epithelial osmoregulation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0952-3278 1532-2823 |
DOI: | 10.1016/j.plefa.2005.07.004 |