Altered cAMP signaling induced by lysophosphatidic acid in senescent human diploid fibroblasts
| Autor: | Kyung A. Cho, Jeong-Soo Park, Eui Ju Yeo, Sang Chul Park, Ji Ae Park, Yong Sung Juhnn, Ik Soon Jang, Jeong Soo Ahn |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Senescence
Gene isoform Aging medicine.medical_specialty Biophysics Receptors Cell Surface Second Messenger Systems Biochemistry Receptors G-Protein-Coupled Adenylyl cyclase chemistry.chemical_compound Internal medicine Lysophosphatidic acid Cyclic AMP medicine Humans Protein Isoforms Receptors Lysophosphatidic Acid Receptor Molecular Biology Cells Cultured biology Phosphoric Diester Hydrolases Cell Biology Fibroblasts Cell biology Endocrinology chemistry Ageing Mitogen-activated protein kinase biology.protein Lysophospholipids Ploidy Adenylyl Cyclases |
| Zdroj: | Biochemical and Biophysical Research Communications. 302:778-784 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/s0006-291x(03)00262-6 |
| Popis: | Lysophosphatidic acid (LPA) is a lipid mitogen that acts through G-protein-coupled receptors. LPA responsiveness has been reported to be dependent on the senescent state of the cells. To solve the mechanism underlying, we observed LPA-dependent cAMP status and found its age-dependent contrasting profile such as high level of cAMP in the senescent cells vs its low level in the young cells. In order to clarify the molecular mechanism of the ageing effect, we examined various molecular species involved in the cAMP signaling pathway by semi-quantitative RT-PCR. EDG-1 and EDG-4 were unchanged, but EDG-2 and EDG-7 were reduced with age. Senescent cells showed a partial reduction of Gi1, Gi2, and Gi3, but no change in the level of Gq. Decreased Gis and Gi-coupled LPA receptors may reduce the inhibitory effect of Gi alpha on adenylyl cyclases (ACs), resulting in cAMP accumulation via activation of adenylyl cyclase in senescent fibroblasts. We also observed an age-dependent increase in some of AC isoforms: II, IV, and VI. In conclusion, multiple changes in the cAMP signaling pathway of the senescent cells might explain the altered responsiveness to the mitogenic stimuli. |
| Databáze: | OpenAIRE |
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