N'-methylnicotinamide blocks activation of normal and leukemic T cell line at an early stage of the cell cycle; role of ADP-ribosylation in the transcription of IL-2
The authors analyzed the role of ADP-ribosyl transferase (ADPRT) in the mitogen induced activation of normal peripheral blood lymphocytes and leukemic T cell line Jurkats through the use of an ADPRT inhibitor. Addition of N'-methylnicotinamide (N'-MN) in the range of 1-10 mM reduced IL-2 production and IL-2 receptor (TAC) expression in both cell specimens in a dose dependent fashion when added before or at the same time as ConA, PHA (+ TPA in Jurkats). When N'-MN was added at different times after mitogens, a sigmoid curve response was obtained. The drug was effective only when added in the early stages of activation (1st 8 hours), causing reduction of viability and cell cycle progression (blast formation-DNA synthesis) and expression of all activation markers such as TAC, OKT-9, OKT-10, and HLA-DR. Late addition of the drug (24 hours or later) had no effect. Exogenous recombinant IL-2 (15 units/ml) partially reversed the N'-MN induced inhibition of /sup 3/H-Thymidine incorporation into DNA from mitogen stimulated normal T cells. Northern blot analysis revealed that N'-MN blocks the transcription of DNA to mRNA coding for IL-2. These data indicate that transcription of the genes involved in immune activation requires ADP-ribosylation of nuclear proteins.
- Research Organization:
- Univ. of California School of Medicine, Los Angeles
- OSTI ID:
- 6859190
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
LYMPHOCYTES
CELL PROLIFERATION
LYMPHOKINES
RECEPTORS
TRANSCRIPTION
NICOTINAMIDE
BIOLOGICAL EFFECTS
TUMOR CELLS
ADP
CELL CYCLE
DNA
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
GENES
LEUKEMIA
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMIDES
ANIMAL CELLS
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DISEASES
GROWTH FACTORS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
MATERIALS
MEMBRANE PROTEINS
MITOGENS
NEOPLASMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRIDINES
PYRIMIDINES
RIBOSIDES
SOMATIC CELLS
VITAMIN B GROUP
VITAMINS
550201* - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques