Requirement of the JNK-associated Bcl-2 pathway for human lactoferrin-induced apoptosis in the Jurkat leukemia T cell line

Shin Hee Lee, Sang Won Park, Chul Woong Pyo, Na Kyung Yoo, Jiyoung Kim, Sang-Yun Choi

Research output: Contribution to journalArticle

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Abstract

The cell proliferation of p53-deficient Jurkat T cells is controlled after prolonged exposure to human lactoferrin (Lf). However, the molecular mechanism by which Lf influences these cellular responses remains unclear. In this study, we demonstrate that Lf-induced apoptosis in Jurkat T cells occurs in a dose- and time-dependent manner via the regulation of c-Jun N-terminal kinase (JNK) activity. Jurkat cells exposed to Lf for 1 day, especially at concentrations in excess of 500 μg/ml, showed typical apoptosis, as indicated by decreased cell viability and increased Annexin V binding. Our results also showed that Lf induced the activation of caspase 9 and caspase 3 activation, as demonstrated by our detection of cleaved caspases and PARP. Lf-induced apoptosis did not influence Bcl-2 expression via an ERK1/2 phosphorylation pathway, but was rather associated with the level of Bcl-2 phosphorylation. The treatment of cells with the specific JNK inhibitor SP600125, but not the p38 MAPK inhibitor SB203580, revealed that the JNK-Bcl-2 signaling cascade is required for Lf-induced apoptosis. When JNK activation was abolished by SP600125, no Bcl-2 phosphorylation was detected, and the Lf-treated Jurkat cells did not undergo cell death. These findings indicate that Lf functions as a biological mediator of apoptosis in the human leukemia Jurkat T-cell line, via the JNK-associated Bcl-2 signaling pathway.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalBiochimie
Volume91
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

Fingerprint

Lactoferrin
T-cells
JNK Mitogen-Activated Protein Kinases
Leukemia
Apoptosis
Jurkat Cells
Cell Line
Phosphorylation
Chemical activation
Mitogen-Activated Protein Kinase 9
Cells
T-Lymphocytes
Caspase 9
MAP Kinase Signaling System
Annexin A5
Cell proliferation
p38 Mitogen-Activated Protein Kinases
Cell death
Caspases
Caspase 3

Keywords

  • Apoptosis
  • Bcl-2
  • JNK
  • Lactoferrin

ASJC Scopus subject areas

  • Biochemistry

Cite this

Requirement of the JNK-associated Bcl-2 pathway for human lactoferrin-induced apoptosis in the Jurkat leukemia T cell line. / Lee, Shin Hee; Park, Sang Won; Pyo, Chul Woong; Yoo, Na Kyung; Kim, Jiyoung; Choi, Sang-Yun.

In: Biochimie, Vol. 91, No. 1, 01.01.2009, p. 102-108.

Research output: Contribution to journalArticle

Lee, Shin Hee ; Park, Sang Won ; Pyo, Chul Woong ; Yoo, Na Kyung ; Kim, Jiyoung ; Choi, Sang-Yun. / Requirement of the JNK-associated Bcl-2 pathway for human lactoferrin-induced apoptosis in the Jurkat leukemia T cell line. In: Biochimie. 2009 ; Vol. 91, No. 1. pp. 102-108.
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