0000000000385445
AUTHOR
Volkmar Günzler
Effects of hydrazyl group containing drugs on leucocyte functions: an immunoregulatory model for the hydralazine-induced lupus-like syndrome.
Isoniazid (INH) and hydralazine (HYD) are transglutaminase (TGase, E.C.2.3.2.13.) substrates containing catalytically recruitable hydrazyl groups. Since they can be expected to inhibit TGase-mediated cell functions by competing with physiological substrates, their effect upon allogeneically and lectin-induced proliferation of mononucleocytes and upon zymosan-induced chemiluminescence of phagocytes was studied. Both compounds inhibited chemiluminescence in a dose-dependent manner. ID50 of HYD was consistently below 20 microM, while that of INH was above 120 microM. Proliferation of immunocompetent cells was suppressed by HYD with an ID50 of 60 microM, INH was inhibitory only above 5000 micro…
Transglutaminase and polyamine dependence of effector functions of human immunocompetent cells
AbstractThe effects of the transglutaminase inhibitor dansyl cadaverine (DC) and the polyamine antagonist methyl glyoxal-bis-(guanylhydrazone) (MeGbG) on the response of lymphocytes towards allogeneic and lectin stimulation and on the zymosan-induced chemiluminescence of neutrophilic granulocytes was studied. Application of DC resulted in dose-dependent suppression of chemiluminiscence and lymphocyte proliferation; no difference of inhibitory potential occurred with variation of incubation time in the latter system. MeGbG was inactive in granulocytes, but inhibited lymphocyte proliferation; its effect increased with time. The experiments provide further evidence for the importance of transg…
The 2-oxoglutarate binding site of prolyl 4-hydroxylase. Identification of distinct subsites and evidence for 2-oxoglutarate decarboxylation in a ligand reaction at the enzyme-bound ferrous ion.
The structure and function of the 2-oxoglutarate binding site of prolyl 4-hydroxylase was studied by assaying the inhibitory potential of 24 selected aliphatic or aromatic compounds. All except one of them inhibited the enzyme competitively with respect to 2-oxoglutarate and noncompetitively with respect to Fe2+, the Ki values ranging from 0.8 microM to over 15 mM. The Ki values for the two most effective inhibitors, pyridine 2,5-dicarboxylate and 2,4-dicarboxylate, were about 0.8 microM and 2 microM, these compounds being the most potent inhibitors of prolyl 4-hydroxylase with respect to 2-oxoglutarate known so far. Only one of the compounds tested, 2-oxoadipinate, was able to support hydr…