REGULATION OF NEURONAL BCL2 PROTEIN EXPRESSION AND CALCIUM HOMEOSTASIS BY TRANSFORMING GROWTH-FACTOR TYPE-BETA CONFERS WIDE-RANGING PROTECTION ON RAT HIPPOCAMPAL-NEURONS

Excessive activation of glutamate receptors accompanied by Ca2+ overlo ading Is thought to be responsible for the death of neurons in various conditions including stroke and epilepsy. Neurons also die if deprive d of important growth factors and trophic influences, conditions sensi tive to certain oncogene products such as the Bcl2 protein. We now dem onstrate that transforming growth factor type beta (TGF-beta) prevents neuronal Ca2+ overloading of rat hippocampal neurons in response to t he glutamatergic agonist N-methyl-D-aspartate or the Ca2+ ionophore 4- Br-A23187 and, in addition, leads to a substantial increase in neurona l Bcl2 protein expression. Parallel cytotoxicity experiments demonstra te 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 insu lts by regulating two factors with great importance for neuronal viabi lity.