Irinotecan-induced ovarian follicular apoptosis is attenuated by deleting the kinase domain of death-associated protein kinase

  • Authors:
    • Li Li
    • Tetsuji Tanaka
    • Kazunori Yukawa
    • Shizuo Akira
    • Naohiko Umesaki
  • View Affiliations

  • Published online on: April 1, 2009     https://doi.org/10.3892/ijo_00000216
  • Pages: 905-914
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Abstract

Although death-associated protein kinase (DAPK) is a Ca2+/calmodulin-regulated serine/threonine kinase that plays important roles in various types of apoptotic cell death, there have been no reports of its tissue distributions and functions in female reproductive organs. By comparing C57BL/6 wild-type mice with DAPK-mutant mice lacking the 74-amino acid catalytic kinase domain of DAPK, the cellular distributions and biological functions of DAPK in murine ovaries were investigated. In situ hybridization analyses with sense and antisense riboprobes revealed that DAPK mRNA was selectively and highly expressed in granulosa cells in the ovaries of both types of mice. There were no significant differences in the body weights, ovarian weights and unstimulated ovarian follicular numbers between the wild-type and DAPK-mutant mice. Intraperitoneal injection of CPT-11, an anticancer topoisomerase I inhibitor that causes granulosa cell-specific apoptosis partly through Fas-Fas ligand (FasL) interactions in MCH mice, induced follicular apoptosis in both the wild-type and DAPK-mutant mice. However, the numbers of apoptotic follicles were significantly reduced in the DAPK-mutant mice. The Fas and FasL expression levels in the CPT-11-injected mice did not differ significantly between the wild-type and DAPK-mutant mice. These results indicate that DAPK positively regulates intracellular signaling pathways for CPT-11-induced granulosa cell apoptosis.

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April 2009
Volume 34 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Li, L., Tanaka, T., Yukawa, K., Akira, S., & Umesaki, N. (2009). Irinotecan-induced ovarian follicular apoptosis is attenuated by deleting the kinase domain of death-associated protein kinase. International Journal of Oncology, 34, 905-914. https://doi.org/10.3892/ijo_00000216
MLA
Li, L., Tanaka, T., Yukawa, K., Akira, S., Umesaki, N."Irinotecan-induced ovarian follicular apoptosis is attenuated by deleting the kinase domain of death-associated protein kinase". International Journal of Oncology 34.4 (2009): 905-914.
Chicago
Li, L., Tanaka, T., Yukawa, K., Akira, S., Umesaki, N."Irinotecan-induced ovarian follicular apoptosis is attenuated by deleting the kinase domain of death-associated protein kinase". International Journal of Oncology 34, no. 4 (2009): 905-914. https://doi.org/10.3892/ijo_00000216