Chlorpromazine inhibits mitochondrial apoptotic pathway via increasing expression of tissue factor. (January 2016)

• Record Type: Journal Article
• Authors: Wu, Jing; Li, Aimei; Li, Yujun; Li, Xiaoguang; Zhang, Qingmeng; Song, Wuqi; Wang, Yao; Ogutu, James O.; Wang, Jindong; Li, Jianbo; Tang, Renkuan; Zhang, Fengmin
• Is Part Of: International journal of biochemistry & cell biology. Volume 70(2016:Jan.)
• Page Start: 82
• Page End: 91
• Publication Date: 2016-01
• Subjects: Chlorpromazine -- Bcl-2 -- Tissue factor -- Neuronal apoptosis -- Mitochondrial apoptotic pathway; CPZ chlorpromazine -- TF tissue factor -- Bcl-2 B-cell lymphoma 2 -- PMI postmortem interval -- CA cornus ammonis -- DG dentate gyrus -- IOD integrated optical density -- IHC immunohistochemistry -- TFPI tissue factor pathway inhibitor -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling -- EGFP enhanced green fluorescence protein -- DMEM Dulbecco's modified eagle medium -- FBS fetal bovine serum -- PMSF protease inhibitor phenylmethylsulfonyl fluoride -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- qRT-PCR quantitative reverse-transcription polymerase chain reaction -- SEM standard error of the mean -- PBS phosphate buffered saline -- DAB diaminobenzidine -- NMDA N-methyl-D-aspartate -- GABA gamma-aminobutyric acid; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.11.008
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: Less apoptotic cells in CPZ-treated schizophrenic brain than in control. Upregulation of TF and Bcl-2 in CPZ-treated schizophrenics. CPZ treatment increases the levels of Bcl-2 and TF in rat brain. Over-expression of TF increases Bcl-2 levels in C6 cells. CPZ inhibits mitochondrial apoptotic pathway by increasing levels of TF. Abstract: Chlorpromazine (CPZ) is a widely used antipsychotic drug with antagonistic effect on dopamine receptors. Accumulating evidence has shown that CPZ plays a neuroprotective role in various models of toxicity and apoptosis. However, the underlying mechanism contributing to this protective effect remains unclear. Here, we evaluate the effect of CPZ on mitochondrial apoptotic pathway in the neuron system. Higher levels of B-cell lymphoma-2 (Bcl-2) and tissue factor (TF) but lower apoptotic rate were found in hippocampus of CPZ-treated schizophrenic patients compared with non-antipsychotic treated controls. Additionally, both short-term and long-term treatment of CPZ in rats could up-regulate the levels of Bcl-2 and TF with no cytotoxic effects. In the in vitro experiment, expression of Bcl-2 was up-regulated in the C6 glioma cells transfected with pEGFP-N1-TF recombinant plasmid. Furthermore, in another independent rat model of apoptosis, compared with the group administrated with alcohol only, the brains of the CPZ-pretreated rats showed lower expression of cleaved caspase-3, cytochrome c and Bax, but higher expression of Bcl-2 and TF. Our data demonstrate that CPZ exerts its neuronal protective effects through inhibiting the activation of mitochondrial apoptotic pathway by up-regulating TF expression, thus providing new insight into CPZ function and application.