Patterns of gene expression associated with recovery and injury in heat-stressed rats

BMC Genomics

Jaques Reifman⁴  John A Lewis⁶  Lisa R Leon³  David A Jackson¹  Bryan G Helwig³  William E Dennis⁶  Christine E Baer⁵  Vineet Rakesh⁴  Danielle L Ippolito²  Jonathan D Stallings⁶ 

[1] Pulmonary Health Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland;Oak Ridge Institute for Science and Education, Fort Detrick, Maryland;Thermal Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts;DoD Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland;Excet, Inc., Fort Detrick, Maryland;Environmental Health Program, U.S. Army Center for Environmental Health Research, Bldg. 568 Doughten Drive, MD 21702-5010 Fort Detrick, Maryland

关键词: Protein aggregation;    Systems biology;    Proteomics;    Transcriptomics;    Heat stress;   

Others  :  1089893
DOI  :  10.1186/1471-2164-15-1058

 received in 2014-06-06, accepted in 2014-11-24,  发布年份 2014

【 摘 要 】

Background

The in vivo gene response associated with hyperthermia is poorly understood. Here, we perform a global, multiorgan characterization of the gene response to heat stress using an in vivo conscious rat model.

Results

We heated rats until implanted thermal probes indicated a maximal core temperature of 41.8°C (T_c,Max). We then compared transcriptomic profiles of liver, lung, kidney, and heart tissues harvested from groups of experimental animals at T_c,Max, 24 hours, and 48 hours after heat stress to time-matched controls kept at an ambient temperature. Cardiac histopathology at 48 hours supported persistent cardiac injury in three out of six animals. Microarray analysis identified 78 differentially expressed genes common to all four organs at T_c,Max. Self-organizing maps identified gene-specific signatures corresponding to protein-folding disorders in heat-stressed rats with histopathological evidence of cardiac injury at 48 hours. Quantitative proteomics analysis by iTRAQ (isobaric tag for relative and absolute quantitation) demonstrated that differential protein expression most closely matched the transcriptomic profile in heat-injured animals at 48 hours. Calculation of protein supersaturation scores supported an increased propensity of proteins to aggregate for proteins that were found to be changing in abundance at 24 hours and in animals with cardiac injury at 48 hours, suggesting a mechanistic association between protein misfolding and the heat-stress response.

Conclusions

Pathway analyses at both the transcript and protein levels supported catastrophic deficits in energetics and cellular metabolism and activation of the unfolded protein response in heat-stressed rats with histopathological evidence of persistent heat injury, providing the basis for a systems-level physiological model of heat illness and recovery.

【 授权许可】

   
2014 Stallings et al.; licensee BioMed Central Ltd.

【 图 表 】

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