Effect of emptying endoplasmic reticulum (ER) calcium stores on neuronal metabolism

Published

Journal Article

In non-neuronal cells, emptying ER calcium stores causes an inhibition of protein synthesis (PS) while leaving the energy state intact, a pattern of changes similar to that produced by transient cerebral ischemia. We, therefore, studied the effect of emptying ER calcium stores on neuronal protein synthesis and energy state, using hippocampal slices prepared from 3-weeks-old rats and neuronal cells isolated from embryonic brains at E19 and held in tissue culture for 9 days. Calcium stores were depleted using caffeine (Ca), an agonist of the ER ryanodine receptor, and thapsigargin (Tg), an ireversible inhibitor of ER calciumATPase. In slices both Ca and Tg produced an about 50% inhibition of PS, the effect of Ca was completely reversed after washing slices, while that of Tg was long-lasting. In neuronal cells Tg blocked PS almost completely and PS recovered only partially after Tg treatment. Tg did not disturbe energy state of cells (ATP levels or energy charge). A 50% inhibition of PS was obtained when neurons were incubated in medium containing 5 nM Tg. Recovery of PS from Tg treatment was significantly hindered when serum was omitted from the medium, suggesting that serum promotes recovery of ER calcium homeostasis. Similar to transient ischemia, Tg-induced inhibition of PS is caused by a blocking of the initiation process (see abstract Doutheil et al.), i.e. a pattern different from that produced by an isolated flooding of cells with calcium ions where the elongation step is inhibited. Further, both Tg-treament and transient ischemia can induce apoptosis. It is, therefore, concluded that posiischemic disturbance in ER calcium homeostasis may contribute to the pathological process of ischémie cell damage. Tg is viewed as a useful tool to study the mechanisms of ischemia-induced disturbances in PS.

Cited Authors

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

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 24 / 4

International Standard Serial Number (ISSN)

  • 0300-5127

Citation Source

  • Scopus