Open AccessRegulation of neuronal Bcl2 protein expression and calcium homeostasis by transforming growth factor type beta confers wide-ranging protection on rat hippocampal neurons.
Author(s) -
Jochen H.M. Prehn,
Vytautas P. Bindokas,
Charles J. Marcuccilli,
Stanisław Krajewski,
John C. Reed,
Richard J. Miller
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.26.12599
Subject(s) - excitotoxicity , glutamate receptor , hippocampal formation , glutamatergic , microbiology and biotechnology , biology , transforming growth factor beta , receptor , programmed cell death , neuroscience , transforming growth factor , chemistry , biochemistry , apoptosis
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 beta (TGF-beta) 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-beta protects rat hippocampal neurons from death induced by excitotoxicity, trophic factor removal, and oxidative injury. Thus, TGF-beta may protect against a wide range of toxic insults by regulating two factors with great importance for neuronal viability.