ANTISENSE INHIBITION OF BAX MESSENGER-RNA INCREASES SURVIVAL OF TERMINALLY DIFFERENTIATED HL60 CELLS

Cell sensitivity to programmed cell death is primarily modulated by me mbers of the Bcl-2 family, as the balance of homodimer or heterodimer formation between proapoptotic and antiapoptotic members defines apopt osis susceptibility in the great majority of cellular contexts. It is, therefore, important to clarify if the Bar protein is limiting for ac tivation of the genetic program of programmed cell death or can be com plemented by different Bcl-2 family members, such as Bah or Bad. To ga in some insight into the role of Bar in the molecular mechanisms of ap optosis of myeloid cells, we inhibited this gene in all-trans-retinoic acid (ATRA)-treated HL60 cells using the methodology of antisense oli godeoxynucleotides (AS-ODN). Our results indicate that Bar inhibition has no effect on the proliferation and differentiation capacity of HL6 0 cells. Instead, the survival rate of terminally differentiated Bar-i nactivated HL60 (Bax((-)) HL60) cells is almost three times higher in respect to control cultures, indicating that in mature granulocytes Ba r is not efficiently complemented by others members of the Bcl-2 famil y proteins.