Publication details

Modulation of death receptor-mediated apoptosis in differentiating human myeloid leukemia HL-60 cells

Authors

VONDRÁČEK Jan SHEARD M.A. KREJČÍ Pavel MINKSOVÁ Kateřina HOFMANOVÁ Jiřina KOZUBÍK Alois

Year of publication 2001
Type Article in Periodical
Magazine / Source Journal of Leukocyte Biology
MU Faculty or unit

Faculty of Science

Citation
Field Physiology
Keywords all-trans retinoic acid; dimethyl sulfoxide; Fas/CD95/APO-1; TNF-alpha; Bcl-2; FAP-1
Description Differentiating myeloid cells may become resistant to various apoptotic stimuli. In the present study, dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA) were found to modulate the sensitivity of HL-60 cells to death receptor-mediated apoptosis in a time-dependent manner. During the early stages of differentiation, DMSO treatment increased the response of HL-60 cells to tumor necrosis factor cw; (TNF-alpha), but enhanced responsiveness was lost during later differentiation stages. In contrast, ATRA treatment induced resistance to TNF-alpha -induced apoptosis, HL-60 cells were resistant to Fas-mediated apoptosis but were sensitized by culturing in serum-free conditions. Similar to its effect on TNF-cr sensitivity, DMSO pretreatment augmented the response to Fas-mediated signaling, which coincided with increased expression of Fas on DMSO-pretreated cells. However, during the later stages of DMSO-induced differentiation, sensitivity to anti-Fas antibody-induced apoptosis declined significantly, although Fas expression was still elevated, The reduced sensitivity to anti-Fas treatment partially correlated with increased Fas-associated phosphatase-l mRNA expression, Thus, regardless of either Fas up-regulation or potentiation of TNF-alpha -mediated apoptosis during early DMSO-induced differentiation, a slow increase in resistance to apoptosis mediated through these death receptors occurs during DMSO-induced differentiation, which contrasts with the rapid induction of resistance following treatment with ATRA.

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