E2F1-directed activation of Bcl-2 is correlated with lactoferrin-induced apoptosis in Jurkat leukemia T lymphocytes |
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Authors: | Shin-Hee Lee Hye-Min Hwang Chul-Woong Pyo Dae Hyun Hahm Sang-Yun Choi |
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Institution: | (1) School of Life Sciences and Biotechnology, Korea University, 5 Anam-dong, Sungbuk-gu, Seoul, 136-701, Korea;(2) Graduate School of East-West Medical Science, Kyung Hee University, Yongin, 446-701, Korea; |
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Abstract: | Lactoferrin (Lf) has been shown to control the proliferation of a variety of mammalian cells. Recently, we reported that human
Lf induces apoptosis via a c-Jun N-terminal kinases (JNK)-associated Bcl-2 pathway that stimulates programmed cell death.
In order to gain insight into the mechanism underlying Lf-triggered apoptotic features, we attempted to determine the mechanisms
whereby the Lf-induced Bcl-2 family proteins exert their pro- or anti-apoptotic effects in Jurkat leukemia T lymphocytes.
Treatment of the cells with high concentrations of Lf resulted in a significant reduction in in vitro growth and cell viability.
As the levels of Lf increased, greater quantities of CDK6 and hyper-phosphorylated retinoblastoma protein were produced, resulting
in the induction of E2F1-dependent apoptosis. Simultaneously, PARP and caspases were efficiently cleaved during Lf-induced
apoptosis. The E2F1-induced apoptotic process occurred preferentially in p53-deficient Jurkat leukemia cells. Therefore, we
attempted to determine whether E2F1-regulated Bcl-2 family proteins involved in the apoptotic process were relevant to Lf-induced
apoptosis. We found that Lf increased the interaction of Bcl-2 with the pro-apoptotic protein Bad, whereas the total protein
levels did not change significantly. Our results, collectively, suggest that Lf exploits the control mechanism of E2F1-regulated
target genes or Bcl-2 family gene networks involved in the apoptotic process in Jurkat human leukemia T lymphocytes. |
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