Integrative metabolome and transcriptome profiling reveals discordant energetic stress between mouse strains with differential sensitivity to acrolein-induced acute lung injury

综合代谢组和转录组分析揭示了对丙烯醛诱发的急性肺损伤具有不同敏感性的小鼠品系之间存在不一致的能量应激

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作者:James P Fabisiak, Mario Medvedovic, Danny C Alexander, Jonathan E McDunn, Vincent J Concel, Kiflai Bein, An Soo Jang, Annerose Berndt, Louis J Vuga, Kelly A Brant, Hannah Pope-Varsalona, Richard A Dopico Jr, Koustav Ganguly, Swapna Upadhyay, Qian Li, Zhen Hu, Naftali Kaminski, George D Leikauf

Conclusion

These findings suggest management of energetic stress varies between these strains, and that the ability to evoke auxiliary energy generating pathways rapidly and effectively may be critical in enhancing survival during acute lung injury in mice.

Results

Using SM/J (sensitive) and 129X1/SvJ (resistant) inbred mouse strains, the lung metabolome was integrated with the transcriptome profile before and after acrolein exposure. A total of 280 small molecules were identified and mean values (log 2 >0.58 or <-0.58, p<0.05) were considered different for between-strain comparisons or within-strain responses to acrolein treatment. At baseline, 24 small molecules increased and 33 small molecules decreased in the SM/J mouse lung as compared to 129X1/SvJ mouse lung. Notable among the increased compounds was malonylcarnitine. Following acrolein exposure, several molecules indicative of glycolysis and branched chain amino acid metabolism increased similarly in both strains, whereas SM/J mice were less effective in generating metabolites related to fatty acid β-oxidation.

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