Pyridine nucleotide analog interference with metabolic processes in mitogen-stimulated human T lymphocytes

Journal Article · Tue Dec 01 00:00:00 EST 1987 · Experimental Cell Research; (United States)

DOI:https://doi.org/10.1016/0014-4827(87)90278-3· OSTI ID:5623430

Berger, S J; Manory, I; Sudar, D C; Krothapalli, D; Berger, N A ^[1]

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1. Case Western Reserve Univ., Cleveland, OH (United States)

The differential metabolic effects of three nicotinamide analogs, 6-aminonicotinamide, 3-aminobenzamide, and 5-methylnicotinamide, were analyzed in mitogen-stimulated preparations of human T lymphocytes. Mitogen stimulation with the phorbol ester TPA and a monoclonal antibody to the T3 cell surface antigen caused an increase in cellular NAD and ATP levels and a marked increase in glucose metabolism as demonstrated by an increase in cellular levels of glucose 6-phosphate and a sevenfold increase in radioactive CO{sub 2} formation from (1-{sup 14}C)glucose. 6-Aminonicotinamide had drastic inhibitory effects on the mitogen-stimulated increases in NAD and ATP levels as well as on the metabolism of glucose. Treatment of the mitogen-stimulated cells with 6-aminonicotinamide also caused a marked increase in cellular levels of 6-phosphogluconate, suggesting inhibition of the hexose monophosphate shunt at 6-phosphogluconate dehydrogenase. Radioactive CO{sub 2} formation from (6-{sup 14}C)glucose showed that metabolism through the tricarboxylic acid cycle was not used to compensate for the inhibition of the hexose monophosphate shunt pathway. Treatment of cells with 3-aminobenzamide had the opposite effect of 6-aminonicotinamide in that cellular NAD levels increased, presumably due to inhibition of poly(ADP-ribose) polymerase.

• OSTI ID: 5623430
• Journal Information: Experimental Cell Research; (United States), Vol. 173:2; ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBON 14 COMPOUNDS
METABOLISM
GLUCOSE
LYMPHOCYTES
CELL PROLIFERATION
MITOGENS
NICOTINAMIDE
NUCLEOTIDE DEHYDROGENASES
PYRIMIDINES
ALDEHYDES
AMIDES
ANIMAL CELLS
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CARBON COMPOUNDS
CONNECTIVE TISSUE CELLS
ENZYMES
HETEROCYCLIC COMPOUNDS
HEXOSES
LABELLED COMPOUNDS
LEUKOCYTES
MATERIALS
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PROTEINS
PYRIDINES
SACCHARIDES
SOMATIC CELLS
VITAMIN B GROUP
VITAMINS
550301* - Cytology- Tracer Techniques