Activation of 2',5'-oligoadenylate synthetase activity on induction of HL-60 leukemia cell differentiation.
A 27-fold increase in 2',5'-oligoadenylate synthetase activity, an enzyme associated with the antiproliferative actions of interferon (IFN), was observed after treatment of HL-60 human leukemia cells with dimethyl sulfoxide (DMSO), an inducer of granulocytic differentiation of the cells. Enzyme activity was elevated after 24 h of exposure to DMSO, was maximal at 48 hours, and declined thereafter. A comparable increase was observed after treatment with 1 U of alpha interferon (IFN-alpha) per ml or 8 U of beta interferon (IFN-beta) per ml. Elevated levels of expression of other IFN-inducible genes, including type I histocompatibility antigen (HLA-B) mRNA and 2',5'-oligoadenylate phosphodiesterase activity, were also observed with DMSO treatment. DMSO-treated HL-60 cells had an increased amount of a 1.8-kilobase mRNA for oligoadenylate [oligo(A)] synthetase when compared with that of control cells; both DMSO- and IFN-treated HL-60 cells also expressed 1.6-, 3.4-, and 4.3-kilobase mRNA. The increase in both oligo(A) synthetase activity and mRNA levels was inhibited by polyclonal antiserum to human IFN-alpha; however, no IFN-alpha mRNA could be detected in the cells. Antiserum to IFN-beta or gamma interferon (IFN-gamma) had no effect on oligo(A) synthetase expression or activity nor was there any detectable IFN-beta 1 or IFN-beta 2 mRNA in the cells. The anti-IFN-alpha serum did not block the elevation of HLA-B mRNA in DMSO-treated cells. These observations suggest that the increased expression of oligo(A) synthetase in DMSO-treated cells may be mediated by the release of an IFN-alpha-like factor; however, the levels of any IFN-alpha mRNA produced in the cells were extremely low.
Schwartz
E L
EL
Department of Oncology, Albert Einstein College of Medicine, Bronx, New York.
Nilson
L A
LA
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005095:Exoribonucleases / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000201:enzymology* / Q000276:immunology / Q000473:pathology
D015235:HLA-B Antigens; D012333:RNA, Messenger; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D005095:Exoribonucleases; C029364:2'-phosphodiesterase; D004121:Dimethyl Sulfoxide