IOVS Hepatology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2006;47:5569-5575.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0333
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow View responses
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luthra, S.
Right arrow Articles by Kenney, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luthra, S.
Right arrow Articles by Kenney, M. C.

Activation of Caspase-8 and Caspase-12 Pathways by 7-Ketocholesterol in Human Retinal Pigment Epithelial Cells

Saurabh Luthra,1,2 Babak Fardin,1,2 Joyce Dong,1 Dieter Hertzog,1 Sami Kamjoo,1 Simon Gebremariam,1 Virit Butani,1 Raja Narayanan,1,3 Jeanie K. Mungcal,1 Baruch D. Kuppermann,1 and M. Cristina Kenney1

1From the Department of Ophthalmology, School of Medicine, University of California, Irvine, California; and the 3L. V. Prasad Eye Institute, Hyderabad, India.

PURPOSE. To determine whether caspase or cathepsin pathways are activated in human retinal pigment epithelial cells (ARPE-19) after exposure to 7-ketocholesterol (7kCh).

METHODS. ARPE-19 cells were exposed to 7kCh with or without z-VAD-fmk, a pan-caspase inhibitor. Caspase-3, -8, and -9 activities were measured by a fluorochrome inhibitor of caspase (FLICA) assay. Caspase-12 activity was detected by Western blotting. RT-PCR was performed for 18s, mortalin-2, cathepsins B, D, and L/V2.

RESULTS. At 24 hours, 7kCh-treated cultures had increased caspase-8 (P < 0.001) and caspase-3 (P < 0.001) activities compared with vehicle-treated cultures. 7kCh-induced caspase-3 activation was blocked by z-VAD-fmk (P < 0.001). Caspase-9 was not activated by 7kCh treatment (P > 0.05). Procaspase-12 was cleaved into its active form after treatment with 7kCh for 24 hours. At 6 hours, the RNA level for mortalin-2, a pro-survival gene, was upregulated. ARPE-19 cells did not express RNA for cathepsins B, D, or L/V2 under any conditions.

CONCLUSIONS. In ARPE-19 cells, 7kCh-induced apoptosis uses the receptor-mediated caspase-8 pathway and the endoplasmic reticulum stress-induced caspase-12 pathway but not the mitochondrial caspase-9 pathway. The cathepsin pathways are not involved in 7kCh-induced cell death. These data demonstrate that 7kCh causes a loss of cell viability through caspase-dependent apoptosis and can act as an oxidative stressor leading to retinal pigment epithelial cell atrophy. Elucidating the specific apoptotic pathways involved may have therapeutic potential for AMD and other retinal diseases.




This article has been cited by other articles:


Home page
 IOVSHome page
M. Chwa, S. R. Atilano, D. Hertzog, H. Zheng, J. Langberg, D. W. Kim, and M. C. Kenney
Hypersensitive Response to Oxidative Stress in Keratoconus Corneal Fibroblasts
Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4361 - 4369.
[Abstract] [Full Text] [PDF]

eLetters:

Read all eLetters

Activation of Caspase-8 and -12 Pathway by 7-Ketocholesterol in Human RPE Cells
Gerard Lizard
IOVS Online, 30 Nov 2007 [Full text]

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the Association for Research in Vision and Ophthalmology