AppppA, heat-shock stress, and cell oxidation.

Abstract

Salmonella typhimurium LT2 induces a set of heat-shock proteins analogous to those found previously in Escherichia coli. These are virtually the only proteins synthesized after a temperature shift from 28.degree. to 50.degree. C. Using a 2-dimensional TLC system developed to resolve adenylylated nucleotides, it was found that S. typhimurium and E. coli accumulate P1,P4-diadenosine-5''-tetraphosphate (AppppA), P1-(adenosine-5'')-P3-(guanosine-3''-diphosphate-5'')-triphosphate (ApppGpp), P1-(adenosine-5'')-P4-(guanosine-5'')-tetraphosphate (AppppG), P1-(adenosine-5'')-P3-(guanosine-5'')-triphosphate (ApppG), and P1,P3-diadenosine-5''-triphosphate (ApppA) after heat shock. These same adenylylated nucleotides accumulate after exposure to ethanol, an agent also known to induce the heat-shock response in a variety of cells. AppppA, ApppGpp, AppppG, ApppG and ApppA were previously shown to accumulate under conditions of oxidation stress. These adenylylated nucleotides may be alarmones, i.e., regulatory molecules, alerting cells to the onset of oxidation stress. The finding that these dinucleotides accumulate in response to heat shock suggests that oxidiation and heat shock have a common physiological effect on cells. These dinucleotides may signal the onset of these stresses and trigger the heat-shock response.