XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
124.
RETINOIC ACID-INDUCED DIffERENTIATION MODULATES THE
APOPTOTIC EffECT OF SODIUM vaLPROATE IN HL-60 CELLS
Jiří Vrba and Jitka Ulrichová
Department of medical chemistry and biochemistry UP Olomouc
Differentiation of myeloid leukemia cells results in resistance to various apoptotic stimuli.
We examined whether human leukemia HL-60 cells differentiating by all-trans retinoic
acid (ATRA) into neutrophil-like phenotype became resistant to the apoptogenic activity
of valproate, an inhibitor of histone deacetylases. In undifferentiated HL-60 cells, valproate
induced the G0/G1 cell cycle arrest and apoptotic changes including dissipation
of the inner mitochondrial membrane potential, loss of plasma membrane asymmetry
and/or integrity, activation of caspase-9 and caspase-3, and appearance of sub-G1 DNA.
Cotreatment with ATRA enhanced the apoptotic response of undifferentiated cells to
valproate. On the other hand, in HL-60 cells pretreated for 72 h with ATRA, valproate in
combination with ATRA induced lower dissipation of mitochondrial membrane potential
and weaker apoptotic changes in the plasma membrane while the DNA fragmentation
was not attenuated in comparison with undifferentiated cells. We conclude that ATRAinduced
differentiation modulates but does not abrogate the apoptotic response of
HL-60 cells to sodium valproate, and nuclei are preferentially affected during apoptosis
of differentiated cells.
Acknowledgements: This research was supported by the Ministry of Education, Youth
and Sports of the Czech Republic (MSM 6198959216).
XXII. Biochemistry Congress, Martin
249