Erp72 expression activated by transient cerebral ischemia or disturbance of neuronal endoplasmic reticulum calcium stores.

Published

Journal Article

Stress-induced activation of the expression of the endoplasmic reticulum (ER)-resident chaperon and member of the protein disulfide isomerase family erp72 was studied after transient cerebral ischemia in vivo using the four-vessel occlusion method and experimental depletion of ER calcium stores in primary neuronal cell cultures. After 8 days in vitro, neurons were exposed to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase, or the Tg solvent DMSO. In separate experiments neurons were pre-loaded with the cell-permeant calcium chelator BAPTA-AM before Tg exposure. Stress-induced changes in erp72 expression were analysed by quantitative PCR. Transient cerebral ischemia produced a significant increase in erp72 mRNA levels which rose to about 200% of control (hippocampus) or 300% of control (cortex). After depletion of ER calcium stores neuronal erp72 mRNA levels rose markedly, peaking at 12 h of recovery. Counteracting the Tg-induced rise in cytoplasmic calcium activity by preloading cells with the chelator BAPTA-AM did not influence erp72 expression significantly, suggesting that the activation of erp72 expression resulted from the depletion of ER calcium stores and not from the corresponding increase in cytoplasmic calcium activity. An activation of erp72 expression is indicative of a disturbance of ER function. The results of the present study therefore provide evidence to support the notion that transient cerebral ischemia induces disturbances of neuronal ER function, probably through a depletion of ER calcium stores.

Full Text

Cited Authors

  • Paschen, W; Gissel, C; Linden, T; Doutheil, J

Published Date

  • March 1, 1998

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 55 - 68

PubMed ID

  • 9570640

Pubmed Central ID

  • 9570640

Electronic International Standard Serial Number (EISSN)

  • 1573-7365

International Standard Serial Number (ISSN)

  • 0885-7490

Digital Object Identifier (DOI)

  • 10.1023/a:1020631029168

Language

  • eng