دورية
IP3, IP3receptor, and cellular senescence
| العنوان: | IP3, IP3receptor, and cellular senescence |
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| المؤلفون: | Huang, Ming-Shyan, Adebanjo, Olugbenga A., Awumey, Emmanuel, Biswas, Gopa, Koval, Antoliy, Sodam, Bali R., Sun, Li, Moonga, Baljit S., Epstein, Joshua, Goldstein, Samuel, Lai, F. Anthony, Lipschitz, David, Zaidi, Mone |
| المصدر: | American Journal of Physiology - Renal Physiology; April 2000, Vol. 278 Issue: 4 pF576-F584, 9p |
| مستخلص: | 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. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 1931857x 15221466 |
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| DOI: | 10.1152/ajprenal.2000.278.4.F576 |