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Updated: Jun 13, 2026
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Published on: July 22, 2021
Effects of AG490 on lens epithelial cell death induced by H(2)O(2)
Ungsoo Samuel Kim1, Sang-Min Nam, Sun-Ah Jung
1Department of Ophthalmology, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Konyang University College of Medicine, Seoul, Korea.
Purpose:
To evaluate the influence of H(2)O(2) 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 H(2)O(2) 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 microM AG490 or 25 microM U0126, LECs were exposed to H(2)O(2). LEC death was evaluated by microscopy and flow cytometry.
Results:
H(2)O(2) 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 microM AG490.
Conclusions:
AG490 may prevent H(2)O(2)-induced LEC death by blocking an unknown necrosis pathway. Further investigation is required to characterize that pathway.
Insights
Hydrogen peroxide (H2O2) causes lens epithelial cell death. The Janus kinase (JAK) inhibitor AG490 protects against H2O2-induced cell death by blocking an unknown necrosis pathway.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Lens epithelial cells (LECs) are crucial for maintaining lens clarity.
- Oxidative stress, induced by hydrogen peroxide (H2O2), can lead to LEC dysfunction and death.
- Understanding the molecular mechanisms of H2O2-induced LEC death is vital for preventing cataracts.
Purpose of the Study:
- To investigate the impact of H2O2 on LECs.
- To assess the protective effects of the Janus kinase (JAK) inhibitor AG490 and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 against H2O2-induced LEC death.
Main Methods:
- Human lens epithelial (HLE) B-3 cells were exposed to H2O2.
- Western blot analysis was used to detect phosphorylation of STAT3, JAK2, and ERK1/2.
- Cells were pretreated with AG490 or U0126 before H2O2 exposure.
- Microscopy and flow cytometry were employed to evaluate LEC death and necrosis.
Main Results:
- H2O2 induced phosphorylation of STAT3, JAK2, and ERK1/2 in LECs.
- AG490 and U0126 suppressed this phosphorylation.
- AG490 significantly enhanced cell survival and decreased necrosis.
- U0126 did not show a significant protective effect on its own.
Conclusions:
- AG490 demonstrates a protective role against H2O2-induced LEC death.
- The protective mechanism of AG490 may involve the inhibition of an unidentified necrosis pathway.
- Further research is needed to fully elucidate the pathway targeted by AG490.
