Open Access

Induction of heme oxygenase-1 and heat shock protein 70 in rat hepatocytes: The role of calcium signaling

  • Malte Silomon1,
  • Inge Bauer1Email author,
  • Michael Bauer1,
  • Julia Nolting1,
  • Markus Paxian1 and
  • Hauke Rensing1
Cellular & Molecular Biology LettersAn International Journal200612:52

https://doi.org/10.2478/s11658-006-0052-0

Received: 20 April 2006

Accepted: 27 July 2006

Published: 13 November 2006

Abstract

Stress response genes including heat shock proteins are induced under a variety of conditions to confer cellular protection. This study investigated the role of calcium signaling in the induction of two stress response genes, heme oxygenase-1/hsp32 and hsp70, in isolated rat hepatocytes. Both genes were induced by cellular glutathione depletion. This induction could be inhibited by BAPTA-AM. Culturing in a calcium-free medium prevented the induction of hsp70 gene expression after glutathione depletion without affecting heme oxygenase-1 gene expression. Thapsigargin increased the gene expression of heme oxygenase-1 but not that of hsp70. Thapsigargin-induced heme oxygenase-1 induction was completely inhibited by BAPTA-AM. Incubation with the Ca2+-ionophore A23187 augmented heme oxygenase-1 (two-fold) and hsp70 (5.2-fold) mRNA levels. Our data suggests a significant role of Ca2+-dependent pathways in the induction of the two stress genes. An increase in the cytoplasmic Ca2+ activity seems to play a key role in the cascade of signaling leading to the induction of the two genes. However, the source of Ca2+ that fluxes into the cytoplasm seems to be different. Our data provides evidence for a compartmentalization of calcium fluxes, i.e. the Ca2+ flux from intracellular stores (e.g. the endoplasmic reticulum) plays a major role in the induction of heme oxygenase-1. By contrast, Ca2+ flux from the extracellular medium seems to be a mechanism initiating the cellular signaling cascade leading to hsp70 gene induction.

Key words

Stress response genes Hepatocytes Calcium Gene expression

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