当前位置: X-MOL 学术Neuropsychopharmacology › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
TSPO upregulation in bipolar disorder and concomitant downregulation of mitophagic proteins and NLRP3 inflammasome activation.
Neuropsychopharmacology ( IF 7.6 ) Pub Date : 2018-12-11 , DOI: 10.1038/s41386-018-0293-4
Giselli Scaini 1 , Tatiana Barichello 1, 2 , Gabriel R Fries 1 , Elizabeth A Kennon 1 , Taylor Andrews 1 , Bobby R Nix 3 , Giovana Zunta-Soares 3 , Samira S Valvassori 4 , Jair C Soares 3, 5 , João Quevedo 1, 3, 4, 5
Affiliation  

Bipolar disorder (BD) is a chronic, debilitating illness with a global prevalence of up to 4.8%. The importance of understanding how dysfunctional mitochondria and mitophagy contribute to cell survival and death in BD is becoming increasingly apparent. Therefore, the purpose of this study was to evaluate the mitophagic pathway and NLRP3 inflammasome activation in peripheral blood mononuclear cells (PBMCs) of patients with BD and healthy individuals. Since 18-kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function and since TSPO itself impairs cellular mitophagy, we also investigated the changes in the TSPO-related pathway. Our results showed that patients with BD had lower levels of Parkin, p62/SQSTM1 and LC3A and an upregulation of TSPO pathway proteins (TSPO and VDAC), both in terms of mRNA and protein levels. Additionally, we found a negative correlation between mitophagy-related proteins and TSPO levels, while VDAC correlated negatively with p62/SQSTM1 and LC3 protein levels. Moreover, we found that the gene expression levels of the NLRP3-related proteins NLRP3, ASC, and pro-casp1 were upregulated in BD patients, followed by an increase in caspase-1 activity as well as IL-1β and IL-18 levels. As expected, there was a strong positive correlation between NLRP3-related inflammasome activation and TSPO-related proteins. The data reported here suggest that TSPO-VDAC complex upregulation in BD patients, the simultaneous downregulation of mitophagic proteins and NLRP3 inflammasome activation could lead to an accumulation of dysfunctional mitochondria, resulting in inflammation and apoptosis. In summary, the findings of this study provide novel evidence that mitochondrial dysfunction measured in peripheral blood is associated with BD.

中文翻译:

双相情感障碍中的TSPO上调以及线粒体蛋白和NLRP3炎性体激活的同时下调。

躁郁症(BD)是一种慢性衰弱性疾病,全球患病率高达4.8%。了解功能障碍的线粒体和线粒体如何促进BD细胞存活和死亡的重要性变得越来越明显。因此,本研究的目的是评估BD患者和健康个体外周血单个核细胞(PBMC)中的线粒体途径和NLRP3炎性小体活化。由于18 kDa转运蛋白(TSPO)在调节线粒体功能中起着重要作用,并且由于TSPO本身会损害细胞的线粒体,因此我们还研究了TSPO相关途径的变化。我们的结果表明,BD患者的mRNA和蛋白质水平均较低,其中Parkin,p62 / SQSTM1和LC3A的水平较低,并且TSPO途径蛋白(TSPO和VDAC)的表达上调。此外,我们发现线粒体相关蛋白与TSPO水平呈负相关,而VDAC与p62 / SQSTM1和LC3蛋白水平呈负相关。此外,我们发现BD患者中NLRP3相关蛋白NLRP3,ASC和pro-casp1的基因表达水平上调,其后caspase-1活性以及IL-1β和IL-18水平升高。正如预期的那样,NLRP3相关的炎性体激活与TSPO相关的蛋白之间存在很强的正相关。此处报道的数据表明,BD患者的TSPO-VDAC复合物上调,线粒体蛋白的同时下调和NLRP3炎性小体激活可能导致功能异常的线粒体积聚,从而导致炎症和细胞凋亡。总之,
更新日期:2019-01-26
down
wechat
bug