αA- and αB-crystallins are distinct antiapoptotic regulators. Regarding the antiapoptotic mechanisms, we have previously demonstrated that under staurosporine treatment, HαA- and HαB-crystallins can interact with Bax and Bcl-XS, proapoptotic members of the Bcl-2 family, to sequester their translocation into mitochondria, and thus prevent the staurosporine-induced apoptosis. In the present study, we further compared the anti-apoptotic mechanisms of HαA- and HαB-crystallin in preventing human lens epithelial cells from UVA-induced apoptosis. UVA-irradiation of human lens epithelial cells turned on the apoptotic death program. Moreover, associated with the activation of the death program, UVA also activated the RAF/MEK/ERK signaling pathway. In contrast, p38 kinase and JNK1/2 signaling pathways were not activated. Inhibition of the RAF/MEK/ERK pathway by a dominant negative mutant RAF1 greatly attenuated UVA-induced apoptosis. Expression of the exogenous human αB-crystallin prevented UVA-induced activation of RAF/MEK/ERK pathway and thus substantially abrogated UVA-induced apoptosis. In contrast, expression of the exogenous human αA-crystallin did not prevent UVA-induced activation of RAF/MEK/ERK pathway. Instead, it activated AKT kinase pathway to promote survival and thus counteracted the UVA-induced apoptosis. Together, our results for the first time reveal that by regulating multiple signaling pathways the two α-crystallins can prevent stress-induced apoptosis through different mechanisms.
Bibliographical noteFunding Information:
This study was supported by the Hormel Foundation, the University of Minnesota Graduate School, and the Lotus Scholars Program Funds from the Ministry of Hunan Province Government and also Hunan Normal University. We thank Dr Venkat Reddy for the human lens epithelial cell line.
- DMEM, Dulbecco's modified Eagle's medium
- ERK1/2, extracellular signal-regulated kinase 1/2
- human lens epithelial cells
- p38 kinase