التفاصيل البيبلوغرافية
| العنوان: |
IP3, IP3 receptor, and cellular senescence |
| المؤلفون: |
Huang, Ming-Shyan, , Olugbenga A. Adebanjo, , Awumey, Emmanuel, Biswas, Gopa, Koval, Antoliy, Sodam, Bali R., §§, Li Sun, ***, , Baljit S. Moonga, , Epstein, Joshua, Goldstein, Samuel, Lai, F. Anthony, Lipschitz, David |
| 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 IP3 formation 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, IP3 formation 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 IP3 receptor protein levels directly in young and senescent HDFs, their microsomal membranes were probed in Western blots with a highly specific anti-IP3 receptor antiserum, Ab40. A ~260-kDa band corresponding to the IP3 receptor protein was noted; its intensity was reduced by ~50% in senescent cells. Thus, we suggest that reduced IP3 receptor expression, lowered IP3 formation, 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 |
