BMP4 Mediates Oxidative Stress-induced Retinal Pigment Epithelial Cell Senescence and Is Overexpressed in Age-related Macular Degeneration
作者： DanHong Zhu , Jian Wu , Christine Spee , Stephen J. Ryan , David R. Hinton
关键词:
摘要: The retinal pigment epithelium is a primary site of pathology in age-related macular degeneration. Oxidative stress and senescence are both thought to be important mediators degeneration pathogenesis. We demonstrate here that bone morphogenetic protein-4 highly expressed the adjacent extracellular matrix patients with dry In vitro studies revealed sublethal oxidative increased expression epithelial cells, persistent mild can induce cell through p53-p21Cip1/WAF1-Rb pathway. further acts as mediator stress-induced this function via Smad p38 signaling pathway increase activate p53 p21Cip1/WAF1 decrease phospho-Rb. blocked by Chordin-like, an antagonist protein-4, or SB203580, phospho-p38 inhibitor. Our results suggest may interact promote represent novel therapeutic target inhibit progressive effects
sci-hub.se 参考文章(70)
Leonard M. Hjelmeland, Behnom Farboud, James T. Handa, Shigeru Honda, Induction of an aging mRNA retinal pigment epithelial cell phenotype by matrix-containing advanced glycation end products in vitro. Investigative Ophthalmology & Visual Science. ,vol. 42, pp. 2419- 2425 ,(2001)
Jong-Tak Kim, Young Seomun, Ji-Young Park, Hae-Sook Kim, Choun-Ki Joo, Induction of p21Cip1-mediated G2/M arrest in H2O2-treated lens epithelial cells. Molecular Vision. ,vol. 11, pp. 764- 774 ,(2005)
Leonard M. Hjelmeland, Amy Aotaki-Keen, Lawrence S. Morse, Gerard A. Lutty, Kazuaki Mishima, James T. Handa, Senescence-associated β-galactosidase histochemistry for the primate eye Investigative Ophthalmology & Visual Science. ,vol. 40, pp. 1590- 1593 ,(1999)
D R Hinton, P F Lopez, B D Sippy, H M Lambert, A B Thach, Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes Investigative Ophthalmology & Visual Science. ,vol. 37, pp. 855- 868 ,(1996)
R. Beyaert, A. Cuenda, W. Vanden Berghe, S. Plaisance, J. C. Lee, G. Haegeman, P. Cohen, W. Fiers, The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. The EMBO Journal. ,vol. 15, pp. 1914- 1923 ,(1996) , 10.1002/J.1460-2075.1996.TB00542.X
Qin M. CHEN, James C. BARTHOLOMEW, Judith CAMPISI, Meileen ACOSTA, Joshua D. REAGAN, Bruce N. AMES, Molecular analysis of H2O2-induced senescent-like growth arrest in normal human fibroblasts: p53 and Rb control G1 arrest but not cell replication. Biochemical Journal. ,vol. 332, pp. 43- 50 ,(1998) , 10.1042/BJ3320043
Wafik S. El-Deiry, Yi Xin Zeng, Regulation of p21WAF1/CIP1 expression by p53-independent pathways. Oncogene. ,vol. 12, pp. 1557- 1564 ,(1996)
R Sanchez-Prieto, J M Rojas, Y Taya, J S Gutkind, A Role for the p38 Mitogen-activated Protein Kinase Pathway in the Transcriptional Activation of p53 on Genotoxic Stress by Chemotherapeutic Agents Cancer Research. ,vol. 60, pp. 2464- 2472 ,(2000)
Paulus T.V.M. de Jong, Mechanisms of disease: Age-related macular degeneration The New England Journal of Medicine. ,vol. 355, pp. 1474- 1485 ,(2006) , 10.1056/NEJMRA062326
Leonard M. Hjelmeland, Amy Aotaki-Keen, Steven W. Sherwood, Hiroshi Matsunaga, James T. Handa, Michael D. West, β-Galactosidase histochemistry and telomere loss in senescent retinal pigment epithelial cells Investigative Ophthalmology & Visual Science. ,vol. 40, pp. 197- 202 ,(1999)