Journal article
Regulation of prostaglandin H synthase‐2 expression in cerebromicrovascular smooth muscle by serum and epidermal growth factor
Journal of cellular physiology, Vol.176(3), pp.495-505
09/1998
DOI: 10.1002/(SICI)1097-4652(199809)176:3<495::AID-JCP6>3.0.CO;2-J
PMID: 9699502
Abstract
Growth factors may play a role in the formation of prostaglandins (PG) by cerebral blood vessels during development or reaction to injury. In smooth muscle cultures isolated from murine cerebral microvessels PG production was induced with either serum or epidermal growth factor (EGF). Prostaglandin H synthase (PGHS) activity peaked at 6 h after the addition of 10% serum or 50 ng/ml EGF. Increases in expression of PGHS‐1 mRNA were small (7‐ to 10‐fold) compared with PGHS‐2 (30‐ to 120‐fold), and the induction patterns were different for serum and EGF. An increase in PGHS‐2 message was detected by 0.5 h of adding either agent, but peak induction occurred earlier for EGF than for serum, 1 h vs. 3 h, respectively. The response to either stimulus had returned to prestimulation levels by 12 h. The induction of PGHS‐2 protein was also transient, but followed a more delayed time course (peak levels at 6 h). Induction of activity, message, and protein by either agent was blocked by 1 μM dexamethasone and attenuated by genistein (100 μM), a nonspecific tyrosine kinase inhibitor. Tyrphostin 47, a more selective EGF receptor tyrosine kinase inhibitor, dose‐dependently inhibited EGF‐stimulated PGHS activity, completely abolishing PG production at 100 μM. However, this inhibitor had no effect on serum‐stimulated PG production. Curiously, 100 μM tyrphostin 47 enhanced EGF‐induced PGHS‐2 mRNA and protein expression. These data suggest that EGF induces the expression of PGHS‐2 in cerebromicrovascular smooth muscle by a mechanism that requires tyrosine kinase activity and that is distinct from serum. J. Cell. Physiol. 176:495–505, 1998. © 1998 Wiley‐Liss, Inc.
Details
- Title: Subtitle
- Regulation of prostaglandin H synthase‐2 expression in cerebromicrovascular smooth muscle by serum and epidermal growth factor
- Creators
- Gretchen RichElizabeth J YoderSteven A Moore
- Resource Type
- Journal article
- Publication Details
- Journal of cellular physiology, Vol.176(3), pp.495-505
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- DOI
- 10.1002/(SICI)1097-4652(199809)176:3<495::AID-JCP6>3.0.CO;2-J
- PMID
- 9699502
- ISSN
- 0021-9541
- eISSN
- 1097-4652
- Number of pages
- 11
- Grant note
- American Heart Association (Grant‐in Aid 96‐50661N) NIH (NS‐27194; NS‐24621; NS‐09858)
- Language
- English
- Date published
- 09/1998
- Academic Unit
- Pathology
- Record Identifier
- 9984046928502771
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