Participation of Pyridinecarboxylic Acids in Endocellular Regulation of Reproduction in Ciliates

Abstract

A comparative study has been performed of effects of a natural chelator of transition metals, picolinic acid (PA) and of its structural analogues: nicotinic (NA), quinaldinic (QA), 2,6- and 3,4-pyridinedicarboxylic (2,6-PDCA, 3,4-PDCA) acids, as well as of synthetic chelators: EDTA and monoethanolaminediacetic acid (MEADAA), on dynamics of proliferation and on glutathione S-transferase (GT) activity in ciliates Tetrahymena pyriformis and Paramecium caudatum. It is revealed that the in vivo cytostatic effect of PA and its complex-forming analogues (QA, 2,6-PDCA) is higher, than of synthetic chelators (EDTA and MEADAA) that have a much higher complex-forming activity. It is shown that PA and its complex-forming analogues (QA and 2,6-PDCA) at a concentration of 1 mM inhibit essentially proliferation in the infusorian cultures. It is shown that the cells at logarithmic growth phase are more sensitive to inhibitory action of all tested compounds, than the cells at stationary phase. It is found that the cytostatic PA effect is associated with disturbance not of DNA replication, but of processes of preparation for the cell division at G2 and D phases of the cell cycle. It is established that the block of cell division both in Tetrahymena pyriformis, and in Paramecium caudatum can be eliminated by addition of 5 mM NADPH to the incubation medium. It is revealed, that PA oppresses essentially the glutathione S-transferase activity in the infusoria of both species. A suggestion is put forward that the cytostatic effect of PA and its complex-forming analogues is due not only to the transition metal chelation and competitive involvement in NAD metabolism, but also to its immediate participation in transmission of proliferative signal, inhibition of nuclear division, and impairment of the glutathione-dependent protective system of cells.