Nicotinamide, a missing link in the early stress response in eukaryotic cells: A hypothesis with special reference to oxidative stress in plants

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.

Ultraviolet‐B‐Radiation‐Induced Changes in Nicotinamide and Glutathione Metabolism and Gene Expression in Plants

“…The components of these routes have previously been shown in other plant species to be involved in gene expression during UV-B-induced or phytochrome-mediated changes (Weisshaar et al, 1991;Bowler et al, 1994;Frohnmeyer et al, 1994), or in association with oxidative stress (Berglund, 1994;Berglund et al, 1996).…”

“…Nicotinamide is also a stress-associated compound which can induce the accumulation of secondary metabolites andlor manifestation of defensive metabolism in plants (Berglund et al, 1993a(Berglund et al, , 1993bBerglund, 1994;Berglund and Ohlsson, 1995). It is also known that nicotinamide can induce defensive metabolism in animal cells (for review see Berglund, 1994).…”

“…For the genes tested (chlorophyll alb-binding protein, chalcone synthase and glutathione reductase) the mRNA levels changed during nicotinamide exposure similarly to the situation in UV-B exposed pea leaves (Strid, 1993). It has been suggested (Berglund, 1994) that nicotinamide, released via the action of poly(ADP-ribose)polymerase, could play an important role as a signal-mediating compound in eukaryotic cells. This could take place during oxidative stress and other events leading to single-strand breaks of DNA, which thereby would influence, for instance, gene expression.…”

Neurobehavioral assessment of hydroalcoholic extract ofTrigonella foenum-graecumseeds in rodent models of Parkinson’s disease

“…n ¼ 6, data were analyzed by Kruskal-Wallis ANOVA followed by Dunn Test separately for each parameter. DOI: 10.3109/13880209.2012.747547 (Saravanan & Pari, 2005;Yen et al, 2005) and functions as a signal transmitter in response to oxidative stress in plants (Berglund, 1994). Further, TGN is a major metabolite of nicotinic acid and is excreted unchanged in urine (Yuyama & Suzuki, 1985) and thus available for protective action on vital organs including neurons.…”

UV‐B‐ and oxidative stress‐induced increase in nicotinamide and trigonelline and inhibition of defensive metabolism induction by poly(ADP‐ribose)polymerase inhibitor in plant tissue

“…It has been hypothesized that nicotinamide (NIC) and/or its metabolites nicotinic acid and N-methyl nicotinic acid (trigonelline; TRIG) may constitute a link between various types of stresses, especially stress causing DNA strand breaks, and the induction of defensive metabolism in eukaryotic cells [9][10][11][12]. An important source of NIC release in response to stress is the DNA strand break-activated eukaryotic enzyme poly(-ADP-ribose)polymerase (PADPRP) [13,14].…”