Etoposide-induced activation of c-jun N-terminal kinase (JNK) correlates with drug-induced apoptosis in salivary gland acinar cells (original) (raw)

Cell Death & Differentiation volume 6, pages 454–462 (1999)Cite this article

Abstract

We have examined the ability of etoposide to induce apoptosis in two recently established rat salivary acinar cell lines. Etoposide induced apoptosis in the parotid C5 cell line as evidenced by the appearance of cytoplasmic blebbing and nuclear condensation, DNA fragmentation and cleavage of PARP. Etoposide also induced activation of c-jun N-terminal kinase (JNK) in parotid C5 cells by 4 h after treatment, with maximal activation at 8–10 h. Coincident with activation of JNK, the amount of activated ERK1 and ERK2 decreased in etoposide-treated parotid C5 cells. In contrast to the parotid C5 cells, the vast majority of submandibular C6 cells appeared to be resistant to etoposide-induced apoptosis. Likewise, activation of JNKs was not observed in etoposide-treated submandibular C6 cells, and the amount of activated ERK1 and ERK2 decreased only slightly. Etoposide treatment of either cell line had no effect upon the activation of p38. Treatment of the parotid C5 cells with Z-VAD-FMK, a caspase inhibitor, inhibited etoposide-induced activation of JNK and DNA fragmentation. These data suggest that etoposide may induce apoptosis in parotid C5 cells by activating JNKs and suppressing the activation of ERKs, thus creating an imbalance in these two signaling pathways.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, 80262, Colorado, USA
    Steven M Anderson & Seija Hunter
  2. Department of Basic Sciences and Oral Research, School of Dentristry, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, 80262, Colorado, USA
    Steven M Anderson, Mary E Reyland, Lynn M Deisher, Kathy A Barzen & David O Quissell

Authors

  1. Steven M Anderson
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  2. Mary E Reyland
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  3. Seija Hunter
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  4. Lynn M Deisher
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  5. Kathy A Barzen
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  6. David O Quissell
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Correspondence toSteven M Anderson.

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Edited by: R.A. Lockshin

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Anderson, S., Reyland, M., Hunter, S. et al. Etoposide-induced activation of c-jun N-terminal kinase (JNK) correlates with drug-induced apoptosis in salivary gland acinar cells.Cell Death Differ 6, 454–462 (1999). https://doi.org/10.1038/sj.cdd.4400507

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