Human αA- and αB-crystallins prevent UVA-induced apoptosis through regulation of PKCα, RAF/MEK/ERK and AKT signaling pathways

Jin Ping Liu, Ryan Schlosser, Wei Ya Ma, Zigang Dong, Hao Feng, Long Liu, Xiao Qing Huang, Yan Liu, David Wan Cheng Li

Research output: Contribution to journalArticle

109 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)393-403
Number of pages11
JournalExperimental Eye Research
Volume79
Issue number3
DOIs
StatePublished - Sep 2004

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Crystallins
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Signaling System
Apoptosis
Staurosporine
Lenses
Epithelial Cells
Mitogen-Activated Protein Kinase 8
Mitochondria
Phosphotransferases
Survival

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

Cite this

Human αA- and αB-crystallins prevent UVA-induced apoptosis through regulation of PKCα, RAF/MEK/ERK and AKT signaling pathways. / Liu, Jin Ping; Schlosser, Ryan; Ma, Wei Ya; Dong, Zigang; Feng, Hao; Liu, Long; Huang, Xiao Qing; Liu, Yan; Li, David Wan Cheng.

In: Experimental Eye Research, Vol. 79, No. 3, 09.2004, p. 393-403.

Research output: Contribution to journalArticle

Liu, Jin Ping ; Schlosser, Ryan ; Ma, Wei Ya ; Dong, Zigang ; Feng, Hao ; Liu, Long ; Huang, Xiao Qing ; Liu, Yan ; Li, David Wan Cheng. / Human αA- and αB-crystallins prevent UVA-induced apoptosis through regulation of PKCα, RAF/MEK/ERK and AKT signaling pathways. In: Experimental Eye Research. 2004 ; Vol. 79, No. 3. pp. 393-403.
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AU - Liu, Jin Ping

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AU - Dong, Zigang

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AU - Liu, Long

AU - Huang, Xiao Qing

AU - Liu, Yan

AU - Li, David Wan Cheng

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AB - 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.

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