Cell Stress and Chaperones

, Volume 15, Issue 5, pp 687–702

A microarray analysis of the effects of moderate hypothermia and rewarming on gene expression by human hepatocytes (HepG2)

  • Larry A. Sonna
  • Matthew M. Kuhlmeier
  • Purvesh Khatri
  • Dechang Chen
  • Craig M. Lilly
Original Paper


The gene expression changes produced by moderate hypothermia are not fully known, but appear to differ in important ways from those produced by heat shock. We examined the gene expression changes produced by moderate hypothermia and tested the hypothesis that rewarming after hypothermia approximates a heat-shock response. Six sets of human HepG2 hepatocytes were subjected to moderate hypothermia (31°C for 16 h), a conventional in vitro heat shock (43°C for 30 min) or control conditions (37°C), then harvested immediately or allowed to recover for 3 h at 37°C. Expression analysis was performed with Affymetrix U133A gene chips, using analysis of variance-based techniques. Moderate hypothermia led to distinct time-dependent expression changes, as did heat shock. Hypothermia initially caused statistically significant, greater than or equal to twofold changes in expression (relative to controls) of 409 sequences (143 increased and 266 decreased), whereas heat shock affected 71 (35 increased and 36 decreased). After 3 h of recovery, 192 sequences (83 increased, 109 decreased) were affected by hypothermia and 231 (146 increased, 85 decreased) by heat shock. Expression of many heat shock proteins was decreased by hypothermia but significantly increased after rewarming. A comparison of sequences affected by thermal stress without regard to the magnitude of change revealed that the overlap between heat and cold stress was greater after 3 h of recovery than immediately following thermal stress. Thus, while some overlap occurs (particularly after rewarming), moderate hypothermia produces extensive, time-dependent gene expression changes in HepG2 cells that differ in important ways from those induced by heat shock.


Cold stress Cell stress response DNA microarray Heat shock proteins 

Supplementary material

12192_2010_181_MOESM1_ESM.doc (502 kb)
ESM 1(DOC 502 kb)


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Copyright information

© Cell Stress Society International 2010

Authors and Affiliations

  • Larry A. Sonna
    • 1
    • 2
  • Matthew M. Kuhlmeier
    • 2
  • Purvesh Khatri
    • 3
  • Dechang Chen
    • 4
  • Craig M. Lilly
    • 5
  1. 1.Division of Pulmonary and Critical Care MedicineUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Thermal and Mountain Medicine DivisionUS Army Research Institute of Environmental MedicineNatickUSA
  3. 3.Department of Computer ScienceWayne State UniversityDetroitUSA
  4. 4.Division of Epidemiology and BiostatisticsUniformed Services University of the Health SciencesBethesdaUSA
  5. 5.Division of Allergy, Pulmonary, and Critical Care Medicine, Department of MedicineUniversity of Massachusetts School of MedicineWorcesterUSA

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