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+ 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.
Prehn
J H
JH
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Bindokas
V P
VP
Marcuccilli
C J
CJ
Krajewski
S
S
Reed
J C
JC
Miller
R J
RJ
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D006706:Homeostasis; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity; D008928:Mitochondria / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D016202:N-Methylaspartate; D007501:Iron; D002118:Calcium