IP3, IP3receptor, and cellular senescence
| Autor: | Mone Zaidi, Samuel Goldstein, Emmanuel M. Awumey, Joshua Epstein, Bali R. Sodam, Antoliy Koval, F. Anthony Lai, Olugbenga A. Adebanjo, Li Sun, Ming-Shyan Huang, Baljit S. Moonga, Gopa Biswas, David A. Lipschitz |
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| Rok vydání: | 2000 |
| Předmět: |
Physiology
Receptors Cytoplasmic and Nuclear Inositol 1 4 5-Trisphosphate Biology Bradykinin chemistry.chemical_compound Cytosol Gene expression medicine Humans Inositol 1 4 5-Trisphosphate Receptors Inositol Child Growth Substances Fibroblast Inositol phosphate Receptor Cells Cultured Cellular Senescence chemistry.chemical_classification Thrombin Fibroblasts Inositol trisphosphate receptor In vitro Cell biology medicine.anatomical_structure Biochemistry chemistry Ageing Calcium Female Calcium Channels Mitogens |
| Zdroj: | American Journal of Physiology-Renal Physiology. 278:F576-F584 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | Herein we demonstrate that replicative cellular senescence in vitro results in sharply reduced inositol 1,4,5-trisphosphate (IP3) receptor levels, reduced mitogen-evoked IP3formation and Ca2+release, and Ca2+store depletion. Human diploid fibroblasts (HDFs) underwent either 30 mean population doublings [mean population doublings (MPDs) thymidine labeling index (TI) >92% (“young”) or between 53 and 58 MPDs (TI < 28%; “senescent”)]. We found that the cytosolic Ca2+release triggered by either ionomycin or by several IP3-generating mitogens, namely bradykinin, thrombin, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF), was attenuated markedly in senescent HDFs. Notably, the triggered cytosolic Ca2+transients were of a smaller magnitude in senescent HDFs. However, the response latency seen with both PDGF and EGF was greater for senescent cells. Finally, a smaller proportion of senescent HDFs showed oscillations. In parallel, IP3formation in response to bradykinin or EGF was also attenuated in senescent HDFs. Furthermore, senescent HDFs displayed a sharply diminished Ca2+release response to intracellularly applied IP3. Finally, to compare IP3receptor protein levels directly in young and senescent HDFs, their microsomal membranes were probed in Western blots with a highly specific anti-IP3receptor antiserum, Ab40. A ∼260-kDa band corresponding to the IP3receptor protein was noted; its intensity was reduced by ∼50% in senescent cells. Thus, we suggest that reduced IP3receptor expression, lowered IP3formation, and Ca2+release, as well as Ca2+store depletion, all contribute to the deficient Ca2+signaling seen in HDFs undergoing replicative senescence. |
| Databáze: | OpenAIRE |
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