The S-oxalin, N-acetyl-S-oxalylcysteamine, inhibits lymphocyte proliferation, IL-2 production and utilization.
S-Oxalins are a recently described class of cell metabolites that appear to function as negative regulators of proliferation. Previously we have shown that exogenous S-oxalylglutathione (GS-Ox) inhibits the proliferation of lymphocytes by inhibiting the production and utilization of IL-2. In the present study the synthetic S-oxalin, N-acetyl-S-oxalylcysteamine (ACS-Ox), was utilized in similar experiments to determine whether GS-Ox itself, or possibly some metabolite formed following initial conversion of GS-Ox by gamma-glutamyltransferase (GGT), is responsible for the effects (ACS-Ox is not metabolized by GGT). ACS-Ox inhibited DNA synthesis in lymphocytes stimulated by concanavalin A similarly to GS-Ox. IL-2 production and utilization and IL-2R expression were inhibited as well. ACS-Ox also inhibited the proliferation of IL-2 dependent cells at the same concentration as GS-Ox. Because the effects of GS-Ox and ACS-Ox are so similar, presumably the S-oxalin itself, rather than some metabolite, is responsible for the observed effects. Transfer of oxalyl groups from S-oxalins to various proteins thiols is the most likely mechanism involved.
Grove
D S
DS
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802, USA.
Crowl
C V
CV
Hamilton
G A
GA
Mastro
A M
AM
D000818:Animals; D001681:Biological Assay; D002417:Cattle; D002478:Cells, Cultured; D003208:Concanavalin A; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*
D007376:Interleukin-2; C099847:N-acetyl-S-oxalylcysteamine; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; C052145:S-oxalylglutathione; D003543:Cysteamine; D005978:Glutathione