HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yang, L.-p. Articles by Tso, M. O. M. Search for Related Content PubMed PubMed Citation Articles by Yang, L.-p. Articles by Tso, M. O. M.

Role of NF-B and MAPKs in Light-Induced Photoreceptor Apoptosis

¹From the Peking University Eye Center, Peking University Third Hospital, Peking University, Beijing, China; and the ²Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

PURPOSE. To elucidate the role of nuclear factor kappa B (NF-B) and mitogen-activated protein kinases (MAPKs) in light-induced apoptosis of photoreceptors in culture and to explore the potential inhibitory effect of minocycline and sulforaphane on apoptosis.

METHODS. Apoptosis of 661W cells was induced by exposure to light and was detected by terminal dUTP transferase nick end labeling (TUNEL). The mRNA expression and protein production of 10 chemokines and noxious factors were examined by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The protein expression of the p65 subunit of NF-B, and the MAPKs p-p38, p-p44/42, and p-JNK were examined by Western blot and immunofluorescence analyses.

RESULTS. After exposure to light for 4 hours, 60% to 70% of the 661W cells underwent apoptosis. The expression of five selected chemokines and noxious factors was upregulated. The protein expression of the p65 subunit of NF-B was downregulated, and the expression of the MAPKs p-p38, p-p44/42, and p-JNK was upregulated. Pretreatment with SB203580 for 1 hour inhibited light-induced upregulation of p-p38 and inhibited photoreceptor apoptosis. Pretreatment with minocycline or sulforaphane for 1 hour inhibited light-induced downregulation of the NF-B p65 subunit and inhibited photoreceptor apoptosis.

CONCLUSIONS. Apoptotic photoreceptors secrete chemokines and noxious factors to induce an immunologic response. The NF-B and MAPK pathways both are involved in light-induced 661W photoreceptor apoptosis. Minocycline and sulforaphane inhibit light-induced photoreceptor apoptosis, partly through an NF-B-dependent mechanism, but not through the MAPK pathway.