No abstract

A hypothesis is presented suggesting that nicotinamide (NIC) is an initial signal substance in the response of eukaryotic cells to conditions which cause DNA-strand breakage, especially in connection with oxidative stress. In the stressed cell, NIC is released as a result of the activity of poly(ADP-ribose)polymerase (PADPRP). PADPRP is known to be activated by DNA-strand breakage, caused by e.g. oxidative stress or mutagens. NIC and its metabolite trigonelline (N-methylnicotinic acid) can induce defensive metabolism at the gene level. Connections between NIC and DNA-methylation are also considered. This hypothesis is discussed in the light of own observations and literature reports.

Nicotinamide and trigoneUine contents increased in

The effects of nicotinamide (NIC) and its natural plant metabolites nicotinic acid (NIA) and trigonelline (TRIG) were studied with respect to defense in plant cell cultures. NIC and NIA could protect against oxidative stress damage caused by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which generates free radicals. Damage was analyzed as DNA strand breaks in cell cultures of Pisum sativum (garden pea), Daucus carota (carrot), Populus tremula L. × P. tremuloides (hybrid aspen) and Catharanthus roseus (Madagascar periwinkle), monitored by single cell gel electrophoresis (comet assay), and assays of cell leakage in C. roseus. The activities of aconitase and fumarase enzymes, which have key roles in energy metabolism, were analyzed in P. sativum cultures after treatment with NIC or NIA. Aconitase activity was increased by NIA, and fumarase activity was increased by both compounds. These compounds were shown to promote glutathione metabolism in P. sativum cultures, and NIC was shown to have a global DNA hypomethylating effect. Neither TRIG nor poly(ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide offered any protection against DNA damage or cell leakage, nor did they promote aconitase or fumarase activities, or glutathione metabolism. By this broad approach addressing multiple biochemical factors and different plant species, we demonstrate that NIC and NIA protect plant cells from oxidative stress, and that NIC clearly exerts an epigenetic effect; decreased DNA methylation. This indicates that these compounds have important roles in the regulation of metabolism in plant cells, especially in connection to stress.