Abstract
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.
Original language | English (US) |
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Pages (from-to) | 393-403 |
Number of pages | 11 |
Journal | Experimental Eye Research |
Volume | 79 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2004 |
Externally published | Yes |
Keywords
- AKT
- DMEM, Dulbecco's modified Eagle's medium
- ERK1/2
- ERK1/2, extracellular signal-regulated kinase 1/2
- JNK1/2
- MEK1/2
- PKCα
- RAF1
- UVA
- apoptosis
- human lens epithelial cells
- p38 kinase
- αA-crystallin
- αB-crystallin
ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience