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Effects of AG490 on lens epithelial cell death induced by H2O2

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Abstract

Purpose

To evaluate the influence of H2O2 on lens epithelial cells (LECs) and to determine the effect of the Janus kinase (JAK) inhibitor AG490 and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 on LEC death after H2O2 exposure.

Methods

Human lens epithelial (HLE) B-3 cells were cultured. Cells were treated for 45 min with H2O2 and signal transducers and activators transcription (STAT) 3, JAK2, and ERK1/2 phosphorylation were surveyed by Western blot analysis. After pretreatment with either 40 μM AG490 or 25 μM U0126, LECs were exposed to H2O2. LEC death was evaluated by microscopy and flow cytometry.

Results

H2O2 induced phosphorylation of Tyr-705 STAT3, JAK2, and ERK1/2 in LECs. In cells pretreated with both AG490 and U0126, phosphorylation of Tyr-705 STAT3, JAK2, and ERK1/2 was suppressed. Microscopic findings, however, showed that only AG490 noticeably enhanced cell survival, and flow cytometry showed that cell necrosis decreased to 4.05% after pretreatment with 40 μM AG490.

Conclusions

AG490 may prevent H2O2-induced LEC death by blocking an unknown necrosis pathway. Further investigation is required to characterize that pathway.

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Authors and Affiliations

  1. Department of Ophthalmology, Kim’s Eye Hospital, Myung-Gok Eye Research Institute, Konyang University College of Medicine, Seoul, Korea

    Ungsoo Samuel Kim & Sung Joo Kim

  2. Department of Ophthalmology, College of Medicine, Yonsei University, Seoul, Korea

    Sang-Min Nam

  3. Kim’s Eye Hospital, Myung-Gok Eye Research Institute, Konyang University College of Medicine, Seoul, Korea

    Sun-Ah Jung & Joon H. Lee

  4. Kim’s Eye Hospital, Myung-Gok Eye Research Institute, Konyang University College of Medicine, Youngdeungpo 4th 156, Youngdeungpo gu, Seoul, 150-034, Korea

    Joon H. Lee

Authors
  1. Ungsoo Samuel Kim
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  2. Sang-Min Nam
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  3. Sun-Ah Jung
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  4. Sung Joo Kim
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  5. Joon H. Lee
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Corresponding author

Correspondence to Joon H. Lee.

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Kim, U.S., Nam, SM., Jung, SA. et al. Effects of AG490 on lens epithelial cell death induced by H2O2 . Jpn J Ophthalmol 54, 151–155 (2010). https://doi.org/10.1007/s10384-009-0772-6

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  • DOI: https://doi.org/10.1007/s10384-009-0772-6

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