XXXX induction during terminal differentiation of friend erythroleukaemia cells correlates with delay of apoptosis and loss of proliferative capacity but not with haemoglobinization.

@entity589 @entity588 @entity1836 @entity8304 @entity3733 @entity619 @entity52729 @entity16747
Friend murine erythroleukaemia (F-MEL) cells are a useful model for studying the processes that regulate erythroid differentiation since exposure of these cells to chemical inducers ( @entity3733 or HMBA) results in commitment to terminal cell division and synthesis of haemoglobin. This study examined the relationship between differentiation and apoptosis in @entity3733 sensitive and resistant F-MEL cells. Clear apoptosis was not observed in @entity3733 -treated sensitive F-MEL (strain 745A) cells during the induction of differentiation. In contrast, @entity3733 -induced 745A cells exhibited delayed apoptosis compared to uninduced cells. Since the @entity588 family members play a major role in the control of apoptosis and/or differentiation, we determined their expression before and after @entity3733 or @entity16747 treatment. Neither untreated nor chemically-induced 745A cells expressed the @entity588 protein. The levels of @entity589 and Bad proteins remained relatively constant during @entity3733 -induced differentiation. @entity3733 or HMBA treatment of 745A cells induced a marked increase of @entity1836 expression during the late phase of differentiation which persisted even when the cells began to die. This upregulation of @entity1836 was independent of cell density but was correlated with cell arrest in G0/G1. @entity3733 treatment induced a similar delay of apoptosis and enhancement of @entity1836 expression in F-MEL (strain TFP10) cells which fail to synthesize haemoglobin in the presence of @entity3733 . @entity619 , which blocks @entity3733 -induced differentiation of F-MEL cells, prevented the induction of @entity1836 . Inhibitors such as @entity8304 or @entity52729 , which inhibit haemoglobin synthesis but not commitment to terminal cell division, did not suppress @entity1836 induction in @entity3733 -induced cells. Taken together, these results indicate that @entity3733 treatment of F-MEL cells induces a marked increase in @entity1836 expression suggesting a role for this anti-apoptotic protein in the process of erythroid differentiation in F-MEL cells. Moreover, induction of @entity1836 during this process seems to be associated with loss of proliferative capacity rather than with haemoglobin synthesis.
