Proc Natl Acad Sci U S A 80(24): 7496-7500

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 degrees C to 50 degrees C. Using a two-dimensional thin-layer chromatographic system developed to resolve adenylylated nucleotides, we have 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. We proposed that 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 oxidation and heat shock have a common physiological effect on cells. We hypothesize that these dinucleotides signal the onset of these stresses and trigger the "heat-shock response."

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Abstract