REGULATION OF NEURONAL BCL2 PROTEIN EXPRESSION AND CALCIUM HOMEOSTASIS BY TRANSFORMING GROWTH-FACTOR TYPE-BETA CONFERS WIDE-RANGING PROTECTION ON RAT HIPPOCAMPAL-NEURONS
REGULATION OF NEURONAL BCL2 PROTEIN EXPRESSION AND CALCIUM HOMEOSTASIS BY TRANSFORMING GROWTH-FACTOR TYPE-BETA CONFERS WIDE-RANGING PROTECTION ON RAT HIPPOCAMPAL-NEURONS
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DOI：
10.1073/pnas.91.26.12599
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发表时间：
1994-12-20
影响因子：
11.1
通讯作者：
MILLER, RJ
中科院分区：
文献类型：
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作者：
PREHN, JHM;BINDOKAS, VP;MILLER, RJ
谷氨酸受体的过度激活伴随着 Ca2+ 超载被认为是导致中风和癫痫等多种疾病中神经元死亡的原因。如果失去重要的生长因子和营养影响，以及对某些致癌基因产物（例如 Bcl2 蛋白）敏感的条件，神经元也会死亡。我们现在证明，β型转化生长因子（TGF-β）可防止大鼠海马神经元对谷氨酸激动剂 N-甲基-D-天冬氨酸或 Ca2+ 离子载体 4-Br-A23187 的反应而导致神经元 Ca2+ 超载，此外，还会导致神经元 Bcl2 蛋白表达的大幅增加。平行细胞毒性实验表明，TGF-β 治疗可保护大鼠海马神经元免受兴奋性毒性、营养因子去除和氧化损伤诱导的死亡。因此，TGF-β可以通过调节对神经元活力非常重要的两个因素来防止多种毒性损伤。
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.