title: Human alphaA- and alphaB-crystallins prevent UVA-induced apoptosis through regulation of PKCalpha, RAF/MEK/ERK and AKT signaling pathways.
abstract: AlphaA- and alphaB-crystallins are distinct antiapoptotic regulators. Regarding the antiapoptotic mechanisms, we have previously demonstrated that under staurosporine treatment, HalphaA- and HalphaB-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 HalphaA- and HalphaB-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 alphaB-crystallin prevented UVA-induced activation of RAF/MEK/ERK pathway and thus substantially abrogated UVA-induced apoptosis. In contrast, expression of the exogenous human alphaA-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 alpha-crystallins can prevent stress-induced apoptosis through different mechanisms.
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin 55912, USA.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Ryan
authors.initials: R
authors.lastname: Schlosser
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Ma
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.forename: Long
authors.initials: L
authors.lastname: Liu
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: David Wan-Cheng
authors.initials: DW
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000528:radiation effects; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction; D014466:Ultraviolet Rays; D038202:alpha-Crystallin A Chain / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism; D038201:alpha-Crystallins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D011518:Proto-Oncogene Proteins; D038202:alpha-Crystallin A Chain; D038203:alpha-Crystallin B Chain; D038201:alpha-Crystallins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases