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Hydrogen peroxide-induced extracellular signal-regulated kinase activation in cultured feline ileal smooth muscle cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Song, Hyun Ju Lee, Tai Sang Jeong, Ji Hoon Min, Y. S. Shin, Chang Yell Sohn, Uy Dong |
| Copyright Year | 2005 |
| Abstract | H(2)O(2) has been shown to act as a signaling molecule involved in many cellular functions such as apoptosis and proliferation. In the present study, we characterized the effects of H(2)O(2) on the activation of mitogen-activated protein (MAP) kinases and examined the factors involved in the process of extracellular signal-regulated kinase (ERK) activation by H(2)O(2) in ileal smooth muscle cells (ISMC). ISMC were cultured and exposed to H(2)O(2). Western blot analysis was performed with phosphospecific MAP kinase antibodies. Potent activation of ERK and moderate activation of stress-activated protein kinase/c-Jun NH(2)-terminal kinase occurred within 30 min of 1 mM H(2)O(2) treatment. However, p38 MAP kinase was not activated by H(2)O(2). The activation of ERK by H(2)O(2) was reduced by the mitogen-activated/ERK-activating kinase inhibitor PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one], Ras inhibitor S-farnesylthiosalicylic acid, removal of extracellular Ca(2+), depletion of the intracellular Ca(2+) pool by thapsigargin, or pretreatment of ISMC with the calmodulin antagonist W-7. Also, H(2)O(2)-induced ERK activation was attenuated by a receptor tyrosine kinase inhibitor, tyrphostin 51, but not by down-regulation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate or by a PKC inhibitor, GF109203X [3-[1-(dimethylaminopropyl)indol-3-yl]-4-(indol-3-yl)maleimide hydrochloride]. Growth factor receptor antagonist suramin pretreatment inhibited H(2)O(2)-induced ERK activation, highlighting a role for growth factor receptors in this activation. Furthermore, the ERK activation by H(2)O(2) was blocked by pretreatment with either N-acetyl-cysteine, o-phenanthroline, or mannitol indicating that metal-catalyzed free radical formation may mediate the initiation of signal transduction by H(2)O(2). These data suggest that short-term stimulation with H(2)O(2) activates the signaling pathways of cell mitogenic effects which are thought to be a protective response against intestinal oxidative stress. |
| Starting Page | 73 |
| Ending Page | 80 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jpet.aspetjournals.org/content/jpet/312/1/391.full.pdf |
| PubMed reference number | 15328380v1 |
| Volume Number | 312 |
| Issue Number | 1 |
| Journal | The Journal of pharmacology and experimental therapeutics |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acetylcysteine Apoptosis Calcium Calmodulin Down-Regulation Free Radical Formation Free Radicals GF 109203X Growth Factor Hydrogen Peroxide Mannitol Mitogens Oxidative Stress PD 98059 Peroxides Phorbols Protein Kinase C Protein Kinases Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor Receptor Protein-Tyrosine Kinases Signal Transduction Smooth muscle (tissue) Suramin Thapsigargin Transcription Initiation Tyrphostins Western Blot antileukoprotease |
| Content Type | Text |
| Resource Type | Article |
