Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/107476
Title: Decrease in equilibrative uridine transport during monocytic differentiation of HL-60 leukaemia: Involvement of protein kinase C
Authors: Lee, C.-W. 
Issue Date: 1994
Source: Lee, C.-W. (1994). Decrease in equilibrative uridine transport during monocytic differentiation of HL-60 leukaemia: Involvement of protein kinase C. Biochemical Journal 300 (2) : 407-412. ScholarBank@NUS Repository.
Abstract: The dose-response curves for the inhibition of equilibrative uridine transport by dilazep, dipyridamole and nitrobenzylthioinosine (NBMPR) in undifferentiated HLr60 cells were biphasic. Some 70% of the transport activity was inhibited with IC50 values of 0.7, 1 and 7 nM respectively. No inhibition of the remaining 30% of transport activity was observed until the dilazep, dipyridamole and NBMPR concentrations exceeded 1, 0.1 and 3 μM respectively. Exposure to phorbol 12-myristate 13-acetate (PMA) for 48 h, to induce monocytic differentiation, caused a 20-fold decrease in V(max) of both NBMPR-sensitive and NBMPR-insensitive equilibrative uridine transport. The decrease in NBMPR-sensitive uridine transport induced by PMA corresponded to a decrease in NBMPR binding sites. A 30% decrease in specific NBMPR binding sites occurred within 6 h of PMA exposure, and could be prevented by uridine and thymidine at concentrations as low as 100 μM, and by staurosporine at 40 nM. However, the protective effects of these compounds diminished with prolonged PMA exposure. No protection was observed with uracil. Exogenous protein kinase C(PKC) in the presence of ATP and PMA decreased the number of specific NBMPR-binding sites in purified HL-60 cell plasma membranes. These results suggest that a PKC-induced conformational change in substrate-binding/transporting site may be responsible for the decrease in NBMPR-sensitive nucleoside transport during PMA-induced monocytic differentiation of HL-60 cells.
Source Title: Biochemical Journal
URI: http://scholarbank.nus.edu.sg/handle/10635/107476
ISSN: 02646021
Appears in Collections:Staff Publications

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