Caspase-independent apoptosis induced by differentiation-inducing factor of Dicytostelium discoideum in INS-1 cells

Caspase-independent apoptosis induced by differentiation-inducing factor of Dicytostelium... Differentiation-inducing factor (DIF) is a lipophilic hormone of Dicytostelium discoideum and has been shown to exert diverse effects in mammalian cells. We investigated the effect of DIF on cell viability in insulin-secreting INS-1 cells. DIF induced cell death in a dose-dependent manner. In DIF-treated cells, nuclear condensation and shrinkage of the cell body were observed. After 6 h of DIF treatment, cells became Tdt-mediated dUTP-biotin nick end-labeling-positive, and DNA ladder formation was detected, indicating that DIF induced apoptosis in these cells. DIF did not activate caspase-3, a key enzyme mediating apoptotic signals generated by various agents. Furthermore, DIF-induced cell death was not affected by Z-asp-2, 6-dichlorobenzoyloxymethylketone, a broad inhibitor of the caspases. As is the case in other types of cells, DIF increased cytoplasmic free calcium concentration in INS-1 cells. However, DIF-induced cell death was not affected by chelating intracellular free calcium by 1, 2-bis(2-aminoophenoxy)ethane- N , N , N , N -tetra acetic acid (BAPTA). These results indicate that DIF induces apoptosis in INS-1 cells by a mechanism independent of caspase-3. DIF-induced elevation of cytoplasmic calcium does not mediate the effect of DIF on cell death. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Caspase-independent apoptosis induced by differentiation-inducing factor of Dicytostelium discoideum in INS-1 cells

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0014-2999
D.O.I.
10.1016/S0014-2999(01)01034-2
Publisher site
See Article on Publisher Site

Abstract

Differentiation-inducing factor (DIF) is a lipophilic hormone of Dicytostelium discoideum and has been shown to exert diverse effects in mammalian cells. We investigated the effect of DIF on cell viability in insulin-secreting INS-1 cells. DIF induced cell death in a dose-dependent manner. In DIF-treated cells, nuclear condensation and shrinkage of the cell body were observed. After 6 h of DIF treatment, cells became Tdt-mediated dUTP-biotin nick end-labeling-positive, and DNA ladder formation was detected, indicating that DIF induced apoptosis in these cells. DIF did not activate caspase-3, a key enzyme mediating apoptotic signals generated by various agents. Furthermore, DIF-induced cell death was not affected by Z-asp-2, 6-dichlorobenzoyloxymethylketone, a broad inhibitor of the caspases. As is the case in other types of cells, DIF increased cytoplasmic free calcium concentration in INS-1 cells. However, DIF-induced cell death was not affected by chelating intracellular free calcium by 1, 2-bis(2-aminoophenoxy)ethane- N , N , N , N -tetra acetic acid (BAPTA). These results indicate that DIF induces apoptosis in INS-1 cells by a mechanism independent of caspase-3. DIF-induced elevation of cytoplasmic calcium does not mediate the effect of DIF on cell death.

Journal

European Journal of PharmacologyElsevier

Published: Jun 8, 2001

References

  • Enforced dimerization of Bax results in its translocation, mitochondrial dysfunction and apoptosis
    Gross, A.; Jockel, J.; Wei, M.C.; Korsmeyer, S.J.
  • Caspase-dependent and independent events in apoptosis induced by hydrogen peroxide
    Kim, D.K.; Cho, E.S.; Um, H.D.

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