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

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.