Sensitivity in vitro of mature and immature mouse thymocytes to dexamethasone cytotoxicity and its correlation to poly ADP-ribosylation.
Mouse thymocytes were fractionated into heavy (subtype I, 79% of total cell number), medium (subtype II, 18%) and light (subtype III, 3%) ones by Percoll density centrifugation and they were identified as immature (subtype I and II) and mature (subtype III) thymocytes based on their proliferative response to mitogens. Whereas the nuclear activity of poly (ADP-ribose) polymerase (EC 2.4.2.30) in the subtype III was only one half that of denser subtypes, it increased two-fold upon mitogen stimulation. The sensitivity of three thymocyte subtypes to the dexamethasone cytotoxicity, as judged by the extent of the DNA cleavage, depletion of NAD and cell viability, was highest in the subtype I and lowest in the subtype III. The possible involvement of poly ADP-ribosylation in the apoptotic (programmed) cell death during intrathymic development of immature to mature thymocytes is discussed.
Hoshino
J
J
Robert Koch-Institute, Biochemistry Department, Berlin, F.R.G.
Beckmann
G
G
Kröger
H
H
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D016922:Cellular Senescence; D002499:Centrifugation, Density Gradient; D003208:Concanavalin A / Q000494:pharmacology; D003907:Dexamethasone / Q000633:toxicity*; D008297:Male; D051379:Mice; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D003208:Concanavalin A; D011064:Poly Adenosine Diphosphate Ribose; D003907:Dexamethasone; D011065:Poly(ADP-ribose) Polymerases; D013755:Tetradecanoylphorbol Acetate