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Actin cytoskeletal architecture regulates nitric oxide-induced apoptosis, dedifferentiation, and cyclooxygenase-2 expression in articular chondrocytes via mitogen-activated protein kinase and protein kinase C pathways.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kim, Song Ja Hwang, Sang-Gu Kim, Ingyu Chun, Jang-Soo |
| Copyright Year | 2003 |
| Abstract | Nitric oxide (NO) in articular chondrocytes regulates differentiation, survival, and inflammatory responses by modulating ERK-1 and -2, p38 kinase, and protein kinase C (PKC) alpha and zeta. In this study, we investigated the effects of the actin cytoskeletal architecture on NO-induced dedifferentiation, apoptosis, cyclooxygenase (COX)-2 expression, and prostaglandin E2 production in articular chondrocytes, with a focus on ERK-1/-2, p38 kinase, and PKC signaling. Disruption of the actin cytoskeleton by cytochalasin D (CD) inhibited NO-induced apoptosis, dedifferentiation, COX-2 expression, and prostaglandin E2 production in chondrocytes cultured on plastic or during cartilage explants culture. CD treatment did not affect ERK-1/-2 activation but blocked the signaling events necessary for NO-induced dedifferentiation, apoptosis, and COX-2 expression such as activation of p38 kinase and inhibition of PKCalpha and -zeta. CD also suppressed activation of downstream signaling of p38 kinase and PKC, such as NF-kappaB activation, p53 accumulation, and caspase-3 activation, which are necessary for NO-induced apoptosis. NO production in articular chondrocytes caused down-regulation of phosphatidylinositol (PI) 3-kinase and Akt activities. The down-regulation of PI 3-kinase and Akt was blocked by CD treatment, and the CD effects on apoptosis, p38 kinase, and PKCalpha and -zeta were abolished by the inhibition of PI 3-kinase with LY294002. Our results collectively indicate that the actin cytoskeleton mediates NO-induced regulatory effects in chondrocytes by modulating down-regulation of PI 3-kinase and Akt, activation of p38 kinase, and inhibition of PKCalpha and -zeta |
| Starting Page | 204 |
| Ending Page | 207 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/early/2003/08/07/jbc.M304887200.full.pdf |
| PubMed reference number | 12907684v1 |
| Volume Number | 278 |
| Issue Number | 43 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anaplasia Apoptosis Cartilage Cell Differentiation process Chondrocyte Cytochalasin D Cytochalasins Cytoskeleton Dinoprostone Down-Regulation Microfilaments Mitogen-Activated Protein Kinases Mitogens Nitric Oxide Prostaglandin E2 Prostaglandin-Endoperoxide Synthase Prostaglandins Protein Kinase C Proto-Oncogene Proteins c-akt caspase-3 cyclooxygenase 2 inflammatory response |
| Content Type | Text |
| Resource Type | Article |
