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The essential role of H2O2 in the regulation of intracellular Ca2+ by epidermal growth factor in Rat-2 fibroblasts
- Source :
- Cellular Signalling. 12:91-98
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- We have investigated a new mechanism by which epidermal growth factor (EGF) increases intracellular Ca(2+) ([Ca(2+)](i)) in Rat-2 fibroblasts. EGF induced a transient increase of [Ca(2+)](i), and sustained Ca(2+) increase disappeared in the absence of extracellular Ca(2+). However, EGF had no effect on the formation of inositol phosphates. Expression of N17Rac or scrape-loading of C3 transferase blocked the elevation of [Ca(2+)](i) by EGF, but not by lysophosphatidic acid (LPA). EGF increased intracellular H(2)O(2), with a maximal increase at 5 min, which was blocked by catalase, scrape-loading of C3 transferase, or expression of N17Rac. H(2)O(2) scavengers, catalase and N-acetyl-L-cysteine, also blocked the Ca(2+) response to EGF, but not to LPA. In the presence of EGTA, preincubation with EGF completely inhibited subsequent Ca(2+) response to extracellular H(2)O(2) and vice versa. Incubation with EGF or phosphatidic acid abolished subsequent elevation of [Ca(2+)](i) by phosphatidic acid or EGF, respectively. Furthermore, preincubation with LPA inhibited the subsequent Ca(2+) response to EGF, but not vice versa. These results suggested that intracellular H(2)O(2) regulated by Rac and RhoA, but not inositol phosphates, was responsible for the EGF-stimulated elevation of [Ca(2+)](i). It was also suggested that EGF cross talked with LPA in the regulation of [Ca(2+)](i) by producing intracellular H(2)O(2).
- Subjects :
- Botulinum Toxins
RHOA
Gene Expression
Cell Line
chemistry.chemical_compound
Epidermal growth factor
Lysophosphatidic acid
Extracellular
Animals
Inositol
Calcium Signaling
ADP Ribose Transferases
Epidermal Growth Factor
biology
Chemistry
Free Radical Scavengers
Hydrogen Peroxide
Receptor Cross-Talk
Cell Biology
Phosphatidic acid
Fibroblasts
Catalase
Oxidants
Molecular biology
Acetylcysteine
Rats
rac GTP-Binding Proteins
EGTA
biology.protein
Calcium
Lysophospholipids
rhoA GTP-Binding Protein
hormones, hormone substitutes, and hormone antagonists
Intracellular
Subjects
Details
- ISSN :
- 08986568
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cellular Signalling
- Accession number :
- edsair.doi.dedup.....08f5ea7b0491109b888cc1f1a604b5eb