Zhu Y, Ahlemeyer B, Bauerbach E, Krieglstein J
Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Ketzerbach 63, D-35032, Marburg, Germany.
Neurochem Int. 2001 Mar;38(3):227-35. doi: 10.1016/s0197-0186(00)00084-x.
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.
转化生长因子β1（TGF-β1）对细胞凋亡的影响因细胞类型、刺激种类及实验条件而异。本研究旨在确定TGF-β1能否在星形孢菌素处理后的大鼠原代海马培养物中预防神经元凋亡并阻断半胱天冬酶-3（caspase-3）的激活。通过台盼蓝排斥试验检测发现，浓度为1和10 ng/ml的TGF-β1显著降低了神经元损伤。用Hoechst 33258进行核染色和TUNEL染色进一步表明，在相同浓度范围内，TGF-β1在星形孢菌素处理24小时后有效减少了神经元凋亡，而0.1 ng/ml的TGF-β1则没有。此外，通过caspase-3活性测定和蛋白质印迹法均表明，TGF-β1（1和10 ng/ml）显著抑制了星形孢菌素诱导的caspase-3激活。本研究提供了证据表明TGF-β1能够有效抑制caspase-3激活，从而保护培养的海马神经元免受凋亡。
