Apoptotic cell death of human T lymphoblastoid cells induced by arginine deiminase.
A growth-inhibitory substance found in the culture of a B-precursor leukemia cell line, NALM-20, was purified from the serum-free culture medium and identified as arginine deiminase derived from Mycoplasma arginini (EC 3.5.3.6). Arginine deiminase strongly inhibited, in a dose-dependent manner, the growth of human T cells and T lymphoblastoid cell lines, but not that of B-precursor and myeloid cell lines. The addition of L-arginine completely restored the growth of T lymphoblastoid cells that had been inhibited by arginine deiminase. The addition of L-ornithine also partially restored it. This enzyme suppressed interleukin-2 (IL-2) production and IL-2 receptor expression in T cells stimulated by non-specific mitogens. The morphologic features of dying cells and DNA fragmentation indicated that arginine deiminase induced apoptotic cell death in T lymphoblasts. Cell cycle analysis revealed that G1-->S transition was blocked in cell treated with arginine deiminase, accompanied by the increase of apoptotic nuclei in the sub-G1 fraction. In conclusion, the deletion of the essential nutrient L-arginine by arginine deiminase significantly inhibited cell growth and activation in T lymphoblasts, accompanied by the induction of apoptotic cell death.
Komada
Y
Y
Department of Pediatrics, Mie University School of Medicine, Japan.
Zhang
X L
XL
Zhou
Y W
YW
Ido
M
M
Azuma
E
E
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology*; D009174:Mycoplasma / Q000201:enzymology; D013601:T-Lymphocytes / Q000473:pathology*
D006867:Hydrolases; C019723:arginine deiminase