Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects.
Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects.
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DOI：
10.1176/ajp.156.12.1895
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发表时间：
1999-12
期刊：
影响因子：
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通讯作者：
G. Pandey;Yogesh K. Dwivedi;S. Pandey;S. Teas;R. Conley;R. Roberts;C. Tamminga
中科院分区：
文献类型：
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作者：
G. Pandey;Yogesh K. Dwivedi;S. Pandey;S. Teas;R. Conley;R. Roberts;C. Tamminga
目的磷脂酰肌醇特异性磷脂酶C（PI-PLC）是磷脂酰肌醇信号转导系统的组成部分。在自杀的成年人和青少年中发现该系统的其他成分异常，因此作者检查了青少年自杀受试者死后大脑中PI-PLC活性和PLC同工酶的蛋白质表达是否异常。方法对18例青少年自杀者和18例正常对照者的脑组织进行了磷脂酰肌醇磷脂酶（PI PLC）活性和磷脂酰肌醇磷脂酶（PLC）β 1、δ 1和γ 1同工酶蛋白表达的检测。通过酶法测定PI-PLC活性，并通过Western印迹技术测定PLC同工酶的蛋白质表达。结果与正常对照组相比，青少年自杀组前额叶皮层第8区和第9区细胞膜和胞浆中磷脂酰肌醇磷脂酶C（PI-PLC）活性和特异性磷脂酰肌醇磷脂酶C β 1同工酶的免疫标记均显著降低。在青少年自杀者的大脑中，PI-PLC活性和PLC β 1同工酶的蛋白质水平之间也有显著的相关性。有精神障碍史的自杀者与无精神障碍史的自杀者的PI-PLC活性和PLC β 1蛋白水平无显著性差异，但两组PI-PLC活性和PLC β 1蛋白表达均显著低于正常人。结论自杀者死后脑组织中PI-PLC活性和PLC β 1同工酶表达水平的降低可能与自杀行为的病理生理学有关。
OBJECTIVE The enzyme phosphoinositide-specific phospholipase C (PI-PLC) is a component of the phosphoinositide signal transduction system. Other components of this system have been found to be abnormal in adults and adolescents who have committed suicide, and so the authors examined whether PI-PLC activity and protein expression of PLC isozymes are abnormal in postmortem brains of teenage suicide subjects. METHOD PI-PLC activity and protein expression of the PLC beta1, delta1, and gamma1 isozymes were examined in Brodmann's areas 8 and 9 of postmortem brains obtained from 18 teenage suicide subjects and 18 matched comparison subjects. PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique. RESULTS Compared with the normal subjects, the teenage suicide subjects had significantly lower PI-PLC activity and immunolabeling of the specific PLC beta1 isozyme in both membrane and cytosol fractions of Brodmann's areas 8 and 9 combined (prefrontal cortex). There was also a significant correlation between PI-PLC activity and protein levels of the PLC beta1 isozyme in the brains of the teenage suicide subjects. There was no significant difference in PI-PLC activity or level of PLC beta1 protein between the suicide subjects with a history of mental disorders and those with no history of mental disorders; however, both groups had significantly lower PI-PLC activity and expression of PLC beta1 protein than the normal subjects. CONCLUSIONS Low PI-PLC activity and expressed levels of the PLC beta1 isozyme in postmortem brains of suicide subjects may have clinical relevance in the pathophysiology of suicidal behavior.