TGF-beta1 inhibits caspase-3 activation and neuronal apoptosis in rat hippocampal cultures.
The effect of TGF-beta1 on apoptosis varies depending on the cell type, the kind of stimulus and the experimental conditions. The present study attempted to identify whether TGF-beta1 can prevent neuronal apoptosis and interrupt caspase-3 activation in rat primary hippocampal cultures after staurosporine treatment. TGF-beta1 at the concentration of 1 and 10 ng/ml significantly reduced neuronal damage as detected by trypan blue exclusion. Nuclear staining with Hoechst 33258 and TUNEL-staining further demonstrated that TGF-beta1 at the same concentration range effectively diminished neuronal apoptosis 24 h after staurosporine treatment, whereas 0.1 ng/ml of TGF-beta1 did not. Furthermore, TGF-beta1 (1 and 10 ng/ml) markedly inhibited the activation of caspase-3 induced by staurosporine as demonstrated by both caspase-3 activity assay and Western blotting. This study provides evidence that TGF-beta1 is able to efficiently inhibit caspase-3 activation, and thereby protects cultured hippocampal neurons against apoptosis.
Zhu
Y
Y
Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Ketzerbach 63, D-35032, Marburg, Germany. zhu@mailer.uni-marburg.de
Ahlemeyer
B
B
Bauerbach
E
E
Krieglstein
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005470:Fluorometry; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344; D019311:Staurosporine / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine