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Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells.

Abstract

Hrk is a newly described proapoptotic member of the Bcl-2 family that is mainly expressed in hematopoietic tissues and cultured neurons. In this study we have examined the expression and activity of Hrk in hematopoietic progenitors. To address these issues, we used 3 growth factor-dependent murine hematopoietic cell lines, HCD-57, FDCP-Mix, and FL5.12. The expression of Hrk was undetectable in cells cultured with growth factors, but it was rapidly up-regulated on growth factor withdrawal. In contrast, the expression of Bcl-x(L) decreased and that of proapoptotic Bax, Bad, and Bak was unchanged or down-regulated after removal of growth factors. This pattern of expression correlated with the induction of apoptosis. Hrk was also up-regulated in human cell lines and in bone marrow-derived CD34(+) cells cultured in the absence of growth factors. In addition, the levels of Hrk were up-regulated after treatment with the chemotherapeutic drug etoposide. Expression of prosurvival Bcl-x(L) or Bcl-2 proteins blocked the induction of Hrk. Hrk was induced in FDCP-Mix cells treated with ionomicin in the presence of IL-3, suggesting that cytosolic calcium may regulate the expression of this proapoptotic protein. Furthermore, ectopic expression of Hrk induced cell death of hematopoietic progenitors in the presence of IL-3. Thus, Hrk is specifically and rapidly induced in hematopoietic progenitors after growth factor deprivation or treatment with chemotherapeutic drugs, and this may be sufficient to induce apoptosis in these cells. (Blood. 2000;95:2742-2747)

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  • Authors+Show Affiliations

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    Servicio de Inmunologia, Hospital Universitario Marques de Valdecilla, INSALUD, Santander, Spain.

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    Source

    Blood 95:9 2000 May 01 pg 2742-7

    MeSH

    Antigens, CD34
    Apoptosis
    Bone Marrow Cells
    Carrier Proteins
    Cell Line
    Cells, Cultured
    Erythropoietin
    Etoposide
    Gene Expression Regulation
    Hematopoietic Stem Cells
    Humans
    Ionomycin
    Membrane Proteins
    Proto-Oncogene Proteins
    Proto-Oncogene Proteins c-bcl-2
    Recombinant Proteins
    Transcription, Genetic
    Transfection
    bcl-2 Homologous Antagonist-Killer Protein
    bcl-2-Associated X Protein
    bcl-Associated Death Protein
    bcl-X Protein

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    10779415

    Citation

    Sanz, C, et al. "Specific and Rapid Induction of the Proapoptotic Protein Hrk After Growth Factor Withdrawal in Hematopoietic Progenitor Cells." Blood, vol. 95, no. 9, 2000, pp. 2742-7.
    Sanz C, Benito A, Inohara N, et al. Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells. Blood. 2000;95(9):2742-7.
    Sanz, C., Benito, A., Inohara, N., Ekhterae, D., Nunez, G., & Fernandez-Luna, J. L. (2000). Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells. Blood, 95(9), pp. 2742-7.
    Sanz C, et al. Specific and Rapid Induction of the Proapoptotic Protein Hrk After Growth Factor Withdrawal in Hematopoietic Progenitor Cells. Blood. 2000 May 1;95(9):2742-7. PubMed PMID: 10779415.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells. AU - Sanz,C, AU - Benito,A, AU - Inohara,N, AU - Ekhterae,D, AU - Nunez,G, AU - Fernandez-Luna,J L, PY - 2000/4/26/pubmed PY - 2000/6/8/medline PY - 2000/4/26/entrez SP - 2742 EP - 7 JF - Blood JO - Blood VL - 95 IS - 9 N2 - Hrk is a newly described proapoptotic member of the Bcl-2 family that is mainly expressed in hematopoietic tissues and cultured neurons. In this study we have examined the expression and activity of Hrk in hematopoietic progenitors. To address these issues, we used 3 growth factor-dependent murine hematopoietic cell lines, HCD-57, FDCP-Mix, and FL5.12. The expression of Hrk was undetectable in cells cultured with growth factors, but it was rapidly up-regulated on growth factor withdrawal. In contrast, the expression of Bcl-x(L) decreased and that of proapoptotic Bax, Bad, and Bak was unchanged or down-regulated after removal of growth factors. This pattern of expression correlated with the induction of apoptosis. Hrk was also up-regulated in human cell lines and in bone marrow-derived CD34(+) cells cultured in the absence of growth factors. In addition, the levels of Hrk were up-regulated after treatment with the chemotherapeutic drug etoposide. Expression of prosurvival Bcl-x(L) or Bcl-2 proteins blocked the induction of Hrk. Hrk was induced in FDCP-Mix cells treated with ionomicin in the presence of IL-3, suggesting that cytosolic calcium may regulate the expression of this proapoptotic protein. Furthermore, ectopic expression of Hrk induced cell death of hematopoietic progenitors in the presence of IL-3. Thus, Hrk is specifically and rapidly induced in hematopoietic progenitors after growth factor deprivation or treatment with chemotherapeutic drugs, and this may be sufficient to induce apoptosis in these cells. (Blood. 2000;95:2742-2747) SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/10779415/Specific_and_rapid_induction_of_the_proapoptotic_protein_Hrk_after_growth_factor_withdrawal_in_hematopoietic_progenitor_cells_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=10779415 DB - PRIME DP - Unbound Medicine ER -