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Glucocorticoid-mediated attenuation of the hsp70 response in trout hepatocytes involves the proteasome

Adrienne N Boone1, Mathilakath M Vijayan

  • 1Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1 Canada.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|August 20, 2002
PubMed

Insights

Elevated cortisol levels reduce heat-shock protein 70 (hsp70) accumulation in trout cells by decreasing hsp70 synthesis. This occurs via proteasome-mediated glucocorticoid receptor (GR) degradation, impacting cellular stress response.

Area of Science:

  • Cellular stress response
  • Molecular biology
  • Fish physiology

Background:

  • Cortisol is a key glucocorticoid in fish, regulating various physiological processes.
  • Heat shock induces cellular stress, triggering the production of heat-shock proteins (hsp70) for cellular protection.
  • The interaction between cortisol and hsp70 response in fish hepatocytes is not fully understood.

Purpose of the Study:

  • To investigate the physiological implications of elevated cortisol on the cellular heat-shock protein 70 (hsp70) response in rainbow trout hepatocytes.
  • To elucidate the molecular mechanisms underlying cortisol's effect on hsp70 accumulation and glucocorticoid receptor (GR) expression.

Main Methods:

  • Primary cultures of rainbow trout hepatocytes were treated with cortisol and subjected to heat shock (+15°C for 1 h).
  • [(35)S]methionine incorporation and pulse-chase experiments were used to assess hsp70 synthesis and degradation.
  • Glucocorticoid receptor (GR) expression was analyzed, and the role of the proteasome was investigated using inhibitors (lactacystin, MG-132).

Main Results:

  • Cortisol treatment significantly reduced hsp70 accumulation following heat shock, primarily due to decreased hsp70 synthesis.
  • Cortisol significantly downregulated glucocorticoid receptor (GR) expression in hepatocytes.
  • Proteasome inhibitors blocked cortisol-induced GR downregulation and enhanced hsp70 expression in heat-shocked cells exposed to cortisol.

Conclusions:

  • Cortisol attenuates the cellular heat-shock response in trout hepatocytes by suppressing hsp70 synthesis.
  • Proteasome-mediated degradation of the glucocorticoid receptor (GR) is a key mechanism by which cortisol exerts its inhibitory effect on the hsp70 response.
  • These findings provide insights into the complex interplay between stress hormones and cellular protective mechanisms in fish.

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