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.
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.
Authors: Amy K L Banes-Berceli; Safia Ogobi; Amany Tawfik; Bela Patel; Amanda Shirley; David M Pollock; David Fulton; Mario B Marrero Journal: Vascul Pharmacol Date: 2005-11 Impact factor: 5.773
Authors: W C Li; J R Kuszak; K Dunn; R R Wang; W Ma; G M Wang; A Spector; M Leib; A M Cotliar; M Weiss Journal: J Cell Biol Date: 1995-07 Impact factor: 10.539