Dysregulation of Protein Kinase C in Adult Depression and Suicide: Evidence From Postmortem Brain Studies.

Dysregulation of Protein Kinase C in Adult Depression and Suicide: Evidence From Postmortem Brain Studies.
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DOI:
10.1093/ijnp/pyab003
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发表时间:
2021-05-18
期刊:
The international journal of neuropsychopharmacology
影响因子:
--
通讯作者:
Ren X
Ren X
中科院分区:
其他
文献类型:
--
作者:
Pandey GN;Sharma A;Rizavi HS;Ren X

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基于对血小板和死后脑PKC及其同工酶的研究,一些证据表明,PKC信号系统异常与情绪障碍和自杀有关。在这项研究中,我们研究了PKC同工酶在抑郁症和自杀中的作用。我们检测了24名正常对照、24名抑郁自杀(DS)和12名抑郁非自杀(DNS)受试者前额皮质区(Brodmann区9)各种PKC同工酶的蛋白和mRNA表达。采用实时定量反转录PCR检测大鼠前额皮质mRNA表达水平,western blotting检测大鼠前额皮质蛋白表达水平。我们观察到,与正常对照组相比,DS和DNS受试者的PKCα、PKCβ i、PKCδ和PKCε mRNA表达显著降低,PKCα、PKCβ i、PKCβ ii和PKCδ同工酶的膜或细胞质部分蛋白表达均降低。目前的研究提供了详细的证据,证明DS和DNS受试者死后大脑中某些PKC同工酶的特异性失调,并进一步支持了PKC在成人和青少年抑郁和自杀人群的血小板和大脑中作用的早期证据。这项全面的研究可能会进一步了解PKC在抑郁症和自杀的病理生理中的作用。
Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study, we examined the role of PKC isozymes in depression and suicide. We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region (Brodmann area 9) in 24 normal control subjects, 24 depressed suicide (DS) subjects, and 12 depressed nonsuicide (DNS) subjects. The levels of mRNA in the prefrontal cortex were determined by quantitative real-time reverse transcription PCR, and the protein expression was determined by western blotting. We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ, and PKCε and decreased protein expression in either the membrane or the cytosol fraction of PKC isozymes PKCα, PKCβI, PKCβII, and PKCδ in DS and DNS subjects compared with normal control subjects. The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of the adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.
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