Regulation of neuronal Bcl2 protein expression and calcium homeostasis by transforming growth factor type β confers wide-ranging protection on rat hippocampal neurons

Jochen H M Prehn, Vytautas P. Bindokas, Charles J. Marcuccilli, Stanislaw Krajewski, John C. Reed, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

Excessive activation of glutamate receptors accompanied by Ca2+ overloading is thought to be responsible for the death of neurons in various conditions including stroke and epilepsy. Neurons also die if deprived of important growth factors and trophic influences, conditions sensitive to certain oncogene products such as the Bcl2 protein. We now demonstrate that transforming growth factor type β (TGF-β) prevents neuronal Ca2+ overloading of rat hippocampal neurons in response to the glutamatergic agonist N-methyl-D-aspartate or the Ca2+ ionophore 4-Br-A23187 and, in addition, leads to a substantial increase in neuronal Bcl2 protein expression. Parallel cytotoxicity experiments demonstrate that treatment with TGF-β protects rat hippocampal neurons from death induced by excitotoxicity, trophic factor removal, and oxidative injury. Thus, TGF-β may protect against a wide range of toxic insults by regulating two factors with great importance for neuronal viability.

Original languageEnglish (US)
Pages (from-to)12599-12603
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number26
DOIs
StatePublished - Dec 20 1994

Keywords

  • apoptosis
  • excitotoxicity
  • growth factor
  • necrosis

ASJC Scopus subject areas

  • General

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