Activation of stress signaling molecules in bat brain during arousal from hibernation

J Neurochem. 2002 Aug;82(4):867-73. doi: 10.1046/j.1471-4159.2002.01022.x.


Induction of glucose-regulated proteins (GRPs) is a ubiquitous intracellular response to stresses such as hypoxia, glucose starvation and acidosis. The induction of GRPs offers some protection against these stresses in vitro, but the specific role of GRPs in vivo remains unclear. Hibernating bats present a good in vivo model to address this question. The bats must overcome local high oxygen demand in tissue by severe metabolic stress during arousal thermogenesis. We used brain tissue of a temperate bat Rhinolopus ferrumequinum to investigate GRP induction by high metabolic oxygen demand and to identify associated signaling molecules. We found that during 30 min of arousal, oxygen consumption increased from nearly zero to 11.9/kg/h, which was about 8.7-fold higher than its active resting metabolic rate. During this time, body temperature rose from 7 degrees C to 35 degrees C, and levels of TNF-alpha and lactate in brain tissue increased 2-2.5-fold, indicating a high risk of oxygen shortage. Concomitantly, levels of GRP75, GRP78 and GRP94 increased 1.5-1.7-fold. At the same time, c-Jun N-terminal protein kinase (JNK) activity increased 6.4-fold, and extracellular signal-regulated protein kinase (ERK) activity decreased to a similar degree (6.1-fold). p38 MAPK activity was very low and remained unchanged during arousal. In addition, survival signaling molecules protein kinase B (Akt) and protein kinase C (PKC) were activated 3- and 5-fold, respectively, during arousal. Taken together, our results showed that bat brain undergoes high oxygen demand during arousal from hibernation. Up-regulation of GRP proteins and activation of JNK, PKCgamma and Akt may be critical for neuroprotection and the survival of bats during the repeated process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal / physiology*
  • Blotting, Western
  • Body Temperature / physiology
  • Brain / metabolism*
  • Carrier Proteins / metabolism
  • Chiroptera / physiology*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins*
  • Hibernation / physiology*
  • JNK Mitogen-Activated Protein Kinases
  • Lactic Acid / metabolism
  • Male
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Chaperones / metabolism
  • Oxygen Consumption / physiology
  • Protein Kinase C / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Stress, Physiological / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases


  • Carrier Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • Proto-Oncogene Proteins
  • Tumor Necrosis Factor-alpha
  • glucose-regulated proteins
  • Lactic Acid
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • molecular chaperone GRP78