Thioredoxin-like 6 protects retinal cell line from photooxidative damage by upregulating NF-kappaB activity.
Apoptosis is the common pathway to photoreceptor cell death in many eye diseases including age-related macular degeneration which affects more than 8 million individuals in the United States alone. RdCVF, a truncated mouse thioredoxin is specifically expressed by rod photoreceptor cells and prevents the apoptosis of cone cells. However the protective mechanism of RdCVF and the implications of its human homologue, thioredoxin-like 6 (TXNL6), on the apoptosis of retinal cells remain unknown. In this study, we examined the function of TXNL6 and investigated its mechanism of protection using a cone photoreceptor cell line, 661W. We found that the photooxidative stress-induced degradation of NF-kappaB proteins is rescued by overexpression of TXNL6, which enabled the NF-kappaB transactivation activity. Furthermore, the overexpression of TXNL6 rescued the photooxidative stress-induced apoptosis of 661W cells. Interestingly, this protective effect was significantly blocked by NF-kappaB specific inhibitors demonstrating that TXNL6 exerts its protective effect against apoptosis via NF-kappaB. Taken together, our study shows that the TXNL6 probably protects retinal cells from photooxidative damage-induced apoptosis via upregulation of NF-kappaB activity. The identification of TXNL6 and the demonstration of its protective mechanism offer new insights into treatment possibilities for photoreceptor cell degradation.
Wang
Xiao Wei
XW
Department of Biological Sciences, National University of Singapore, 117543 Singapore.
Tan
Bao Zhen
BZ
Sun
Miao
M
Ho
Bow
B
Ding
Jeak Ling
JL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D016328:NF-kappa B; C488098:NXNL1 protein, human; D017382:Reactive Oxygen Species; D013879:Thioredoxins