Apoptotic cell death of human T lymphoblastoid cells induced by arginine deiminase
Y. Komada, X-L. Zhang, Y-W. Zhou, M. Ido and E. AzumaInternational Journal of Hematology (1997), Vol. 65 pages 129-141
A growth-inhibitory substance found in the culture of a B-precursor leukemia cell line, NALM-20, was purified from the serum-free medium and was 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 the 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) 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 cells treated with arginine deiminase, accompanied by the increase of apoptotic nuclei in the sub-G1 fraction. In conclusion, the depletion 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.