|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 113, Issue 20 3613-3622, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
DJ Kurz, S Decary, Y Hong and JD Erusalimsky
Cell Biology Group, Centre for Cardiovascular Biology and Medicine, Department of Medicine, Royal Free and University College Medical School, University College London, London WC1E 6JJ, UK. erusalimsky@ucl.ac.uk.
Senescence-associated (beta)-galactosidase is widely used as a biomarker of replicative senescence. However, it remains unknown whether this is a distinct enzyme active at pH 6, and differentially expressed in senescence, or a manifestation of an increase in the classic acid lysosomal (beta)-galactosidase. Here we have investigated the origin of senescence-associated-(beta)-galactosidase activity by modifying the intracellular and lysosomal pH of young and senescent human umbilical vein endothelial cells and examining the effect of these manipulations on the levels of activity, using a flow cytometric assay. Lysosomal alkalinisation with chloroquine or bafilomycin A(1), as well as equilibration of the intracellular milieu to pH 6 with nigericin, caused a profound (92-99%) inhibition of the total intracellular (beta)-galactosidase activity. However, independent of pH alterations, senescent cells showed levels of (beta)-galactosidase activity three- to sixfold higher than young cells. This increase in activity occurred in parallel to an increase in (beta)-galactosidase protein levels. Acridine Orange staining revealed an increase in lysosomal content with replicative age, which correlated with the increase in (beta)-galactosidase. These findings demonstrate that senescence-associated (beta)-galactosidase is a manifestation of residual lysosomal activity at a suboptimal pH, which becomes detectable due to the increased lysosomal content in senescent cells.
This article has been cited by other articles:
![]() |
S.-C. Shih, A. Zukauskas, D. Li, G. Liu, L.-H. Ang, J. A. Nagy, L. F. Brown, and H. F. Dvorak The L6 Protein TM4SF1 Is Critical for Endothelial Cell Function and Tumor Angiogenesis Cancer Res., April 15, 2009; 69(8): 3272 - 3277. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Erusalimsky and C. Skene Mechanisms of endothelial senescence Exp Physiol, March 1, 2009; 94(3): 299 - 304. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Erusalimsky Vascular endothelial senescence: from mechanisms to pathophysiology J Appl Physiol, January 1, 2009; 106(1): 326 - 332. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-Y. Hsu, Y.-C. Chiu, W.-L. Hsu, and Y.-P. Chan Age-Related Markers Assayed at Different Developmental Stages of the Annual Fish Nothobranchius rachovii J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2008; 63(12): 1267 - 1276. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Chesnokova, S. Zonis, K. Kovacs, A. Ben-Shlomo, K. Wawrowsky, S. Bannykh, and S. Melmed p21Cip1 restrains pituitary tumor growth PNAS, November 11, 2008; 105(45): 17498 - 17503. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. B. Liton, Y. Lin, C. Luna, G. Li, P. Gonzalez, and D. L. Epstein Cultured Porcine Trabecular Meshwork Cells Display Altered Lysosomal Function When Subjected to Chronic Oxidative Stress Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 3961 - 3969. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Patschan, J. Chen, A. Polotskaia, N. Mendelev, J. Cheng, D. Patschan, and M. S. Goligorsky Lipid mediators of autophagy in stress-induced premature senescence of endothelial cells Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1119 - H1129. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Xue, H. Nolla, A. Suzuki, T. W. Mak, and A. Winoto Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice PNAS, February 12, 2008; 105(6): 2022 - 2027. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Patschan, J. Chen, O. Gealekman, K. Krupincza, M. Wang, L. Shu, J. A. Shayman, and M. S. Goligorsky Mapping mechanisms and charting the time course of premature cell senescence and apoptosis: lysosomal dysfunction and ganglioside accumulation in endothelial cells Am J Physiol Renal Physiol, January 1, 2008; 294(1): F100 - F109. [Abstract] [Full Text] [PDF] |
||||
![]() |
Q. Shi, G. B. Hubbard, R. S. Kushwaha, D. Rainwater, C. A. Thomas III, M. M. Leland, J. L. VandeBerg, and X. L. Wang Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2913 - H2920. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Johung, E. C. Goodwin, and D. DiMaio Human Papillomavirus E7 Repression in Cervical Carcinoma Cells Initiates a Transcriptional Cascade Driven by the Retinoblastoma Family, Resulting in Senescence J. Virol., March 1, 2007; 81(5): 2102 - 2116. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Hatanaka, Y. Hatanaka, J.-i. Tsuchida, V. Ganapathy, and M. Setou Amino Acid Transporter ATA2 Is Stored at the trans-Golgi Network and Released by Insulin Stimulus in Adipocytes J. Biol. Chem., December 22, 2006; 281(51): 39273 - 39284. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Nyunoya, M. M. Monick, A. Klingelhutz, T. O. Yarovinsky, J. R. Cagley, and G. W. Hunninghake Cigarette Smoke Induces Cellular Senescence Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 681 - 688. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Gorenne, M. Kavurma, S. Scott, and M. Bennett Vascular smooth muscle cell senescence in atherosclerosis Cardiovasc Res, October 1, 2006; 72(1): 9 - 17. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Matthews, I. Gorenne, S. Scott, N. Figg, P. Kirkpatrick, A. Ritchie, M. Goddard, and M. Bennett Vascular Smooth Muscle Cells Undergo Telomere-Based Senescence in Human Atherosclerosis: Effects of Telomerase and Oxidative Stress Circ. Res., July 21, 2006; 99(2): 156 - 164. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Mimura and N. C. Joyce Replication competence and senescence in central and peripheral human corneal endothelium. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1387 - 1396. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Chernova, P. Nicotera, and A. G. Smith Heme Deficiency Is Associated with Senescence and Causes Suppression of N-Methyl-D-aspartate Receptor Subunits Expression in Primary Cortical Neurons Mol. Pharmacol., March 1, 2006; 69(3): 697 - 705. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Tsuji, K. Aoshiba, and A. Nagai Cigarette Smoke Induces Senescence in Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., December 1, 2004; 31(6): 643 - 649. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Kurz, S. Decary, Y. Hong, E. Trivier, A. Akhmedov, and J. D. Erusalimsky Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells J. Cell Sci., May 1, 2004; 117(11): 2417 - 2426. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Melk Senescence of renal cells: molecular basis and clinical implications Nephrol. Dial. Transplant., December 1, 2003; 18(12): 2474 - 2478. [Full Text] [PDF] |
||||
![]() |
A. Ruiz-Torres, R. Lozano, J. Melon, and R. Carraro Age-Dependent Decline of In Vitro Migration (Basal and Stimulated by IGF-1 or Insulin) of Human Vascular Smooth Muscle Cells J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2003; 58(12): B1074 - 1077. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Aoshiba, T. Tsuji, and A. Nagai Bleomycin induces cellular senescence in alveolar epithelial cells Eur. Respir. J., September 1, 2003; 22(3): 436 - 443. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. B. Roninson Tumor Cell Senescence in Cancer Treatment Cancer Res., June 1, 2003; 63(11): 2705 - 2715. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Kurz, Y. Hong, E. Trivier, H.-L. Huang, S. Decary, G. H. Zang, T. F. Luscher, and J. D. Erusalimsky Fibroblast Growth Factor-2, But Not Vascular Endothelial Growth Factor, Upregulates Telomerase Activity in Human Endothelial Cells Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 748 - 754. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Joosten, V. van Ham, C. E. Nolan, M. C. Borrias, A. G. Jardine, P. G. Shiels, C. van Kooten, and L. C. Paul Telomere Shortening and Cellular Senescence in a Model of Chronic Renal Allograft Rejection Am. J. Pathol., April 1, 2003; 162(4): 1305 - 1312. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Ono, S. O. Kim, and J. Han Susceptibility of Lysosomes to Rupture Is a Determinant for Plasma Membrane Disruption in Tumor Necrosis Factor Alpha-Induced Cell Death Mol. Cell. Biol., January 15, 2003; 23(2): 665 - 676. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. Deshpande, B. Qi, Y. C. Park, and K. Irani Constitutive Activation of rac1 Results in Mitochondrial Oxidative Stress and Induces Premature Endothelial Cell Senescence Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): e1 - 6. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Erusalimsky, M. Fenton, T. Minamino, H. Miyauchi, T. Yoshida, I. Komuro, Y. Ishida, and H. Yoshida Further In Vivo Evidence That Cellular Senescence Is Implicated in Vascular Pathophysiology * Response Circulation, November 12, 2002; 106 (20): e144 - e144. [Full Text] [PDF] |
||||
![]() |
M. Fenton, S. Barker, D. J. Kurz, and J. D. Erusalimsky Cellular Senescence After Single and Repeated Balloon Catheter Denudations of Rabbit Carotid Arteries Arterioscler Thromb Vasc Biol, February 1, 2001; 21(2): 220 - 226. [Abstract] [Full Text] [PDF] |
||||