BIOMAT Database Logo BIOMAT Database Logo

3-Deazaadenosine. S-adenosylhomocysteine hydrolase-independent mechanism of action in mouse lymphocytes. 1984

T P Zimmerman, and M Iannone, and G Wolberg

3-Deazaadenosine (c3Ado) inhibits the ability of specifically sensitized mouse lymphocytes to lyse tumor cells, and this effect of c3Ado on immune function is accompanied by a buildup of both S-adenosylhomocysteine (AdoHcy) and S-3-deazaadenosylhomocysteine (c3AdoHcy) within the lymphocytes (Zimmerman, T. P., Wolberg, G., and Duncan, G. S. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 6220-6224). Several types of evidence have now been obtained which indicate that neither of these latter two biochemical events contributes to this biological activity of c3Ado. First, periodate-oxidized adenosine (Adox) and 3-deaza(+/-)aristeromycin, two compounds which are not inhibitory to this lymphocyte function, were both more effective than c3Ado in elevating lymphocyte AdoHcy levels and in inhibiting protein carboxymethylation within these cells. Second, pretreatment of lymphocytes with Adox (to inhibit AdoHcy hydrolase) prevented the metabolic formation of c3AdoHcy during subsequent incubation of the cells with c3Ado without diminishment of the biological activity of c3Ado. Third, the lymphocyte buildup of c3AdoHcy exhibited a concentration dependence upon c3Ado which was biphasic and greatly dissimilar to that for the inhibition of lymphocyte function by c3Ado. These results are not compatible with the widely held view that c3Ado, as a single agent, affects various cellular functions as a consequence of elevations in intracellular AdoHcy and/or c3AdoHcy and suggest that c3Ado inhibits this particular lymphocyte function by an unknown mechanism which is independent of the interaction of c3Ado with AdoHcy hydrolase. During this study, it was found that pretreatment of lymphocytes with Adox prevented the potentiation by homocysteine of this immunoinhibitory activity of c3Ado and reduced the biological effect of the c3Ado/homocysteine combination to that observed with c3Ado alone. This result indicates that the ability of homocysteine to potentiate this biological activity of c3Ado requires the metabolic formation of c3AdoHcy catalyzed by AdoHcy hydrolase.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D006867 Hydrolases Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3. Hydrolase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012263 Ribonucleosides Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
D012435 S-Adenosylhomocysteine 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. S Adenosylhomocysteine,Adenosylhomocysteine, S
D014372 Tubercidin An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids. 7-Deazaadenosine,4-Amino-7 beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)pyrimidine,Deazaadenosine,7 Deazaadenosine
D043383 Adenosylhomocysteinase An enzyme which catalyzes the catabolism of S-ADENOSYLHOMOCYSTEINE to ADENOSINE and HOMOCYSTEINE. It may play a role in regulating the concentration of intracellular adenosylhomocysteine. S-adenosylhomocysteine Hydrolase,S-adenosylhomocysteine Synthase,SAH Hydrolase,Hydrolase, S-adenosylhomocysteine,S adenosylhomocysteine Hydrolase,S adenosylhomocysteine Synthase
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

T P Zimmerman, and M Iannone, and G Wolberg
Immunosuppressive effects of the S-adenosylhomocysteine hydrolase inhibitor, 3-deazaadenosine.
January 1982, Journal of immunopharmacology,
T P Zimmerman, and M Iannone, and G Wolberg
The action of the adenosylhomocysteine hydrolase inhibitor, 3-deazaadenosine, on phagocytic function of mouse macrophages and human monocytes.
September 1978, Biochemical and biophysical research communications,
T P Zimmerman, and M Iannone, and G Wolberg
Effects of the S-adenosylhomocysteine hydrolase inhibitors 3-deazaadenosine and 3-deazaaristeromycin on RNA methylation and synthesis.
October 1986, European journal of biochemistry,
T P Zimmerman, and M Iannone, and G Wolberg
Carbocyclic analogue of 3-deazaadenosine: a novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target.
June 1982, Journal of medicinal chemistry,
T P Zimmerman, and M Iannone, and G Wolberg
Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 8. Molecular dissections of carbocyclic 3-deazaadenosine as inhibitors of S-adenosylhomocysteine hydrolase.
April 1985, Journal of medicinal chemistry,
T P Zimmerman, and M Iannone, and G Wolberg
Modulation of cyclic AMP metabolism by S-adenosylhomocysteine and S-3-deazaadenosylhomocysteine in mouse lymphocytes.
October 1980, Proceedings of the National Academy of Sciences of the United States of America,
T P Zimmerman, and M Iannone, and G Wolberg
3-Deazaadenosine, an S-adenosylhomocysteine hydrolase inhibitor, attenuates lipopolysaccharide-induced inflammatory responses via inhibition of AP-1 and NF-κB signaling.
December 2020, Biochemical pharmacology,
T P Zimmerman, and M Iannone, and G Wolberg
S-Adenosylhomocysteine hydrolase as a target for intracellular adenosine action.
June 2004, Trends in pharmacological sciences,
T P Zimmerman, and M Iannone, and G Wolberg
Pharmacological and biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase.
September 1982, Pharmacological reviews,
T P Zimmerman, and M Iannone, and G Wolberg
S-adenosylhomocysteine hydrolase, S-adenosylmethionine, S-adenosylhomocysteine: correlations with ribavirin induced anemia.
January 2004, Medical hypotheses,
Copied contents to your clipboard!