Bioinformatic analysis of differentially expressed proteins in the dorsal raphe nucleus of rats after continuous treatment with olanzapine.
10.12122/j.issn.1673-4254.2022.08.15
- Author:
Ping HUANG
1
;
Jian Cheng ZHU
1
;
Hua LI
1
;
Yan Zhao WANG
1
;
Yi Min TANG
1
;
Qiang LIU
1
Author Information
1. Department of Endocrinology, Jiujiang Fifth People's Hospital, Jiujiang 332000, China.
- Publication Type:Journal Article
- Keywords:
bioinformatics;
dorsal raphe nucleus;
iTRAQ technology;
metabolic disorders;
olanzapine;
serotonergic synapse pathway
- MeSH:
Animals;
Chromatography, Liquid;
Computational Biology;
Dorsal Raphe Nucleus;
Female;
GTP-Binding Protein alpha Subunits, Gi-Go;
Male;
Mice;
Olanzapine/adverse effects*;
Proteomics;
Rats;
Rats, Sprague-Dawley;
Tandem Mass Spectrometry
- From:
Journal of Southern Medical University
2022;42(8):1221-1229
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the differentially expressed proteins in the dorsal raphe nucleus of rats treated with olanzapine and explore the possible mechanism of metabolic disorders in the early stage of olanzapine treatment.
METHODS:Twenty male and 20 female SD rats were both randomized equally into olanzapine group and control group for daily treatment with olanzapine and saline for 4 weeks, respectively. One hour after the last treatment, the dorsal raphe nucleus of the rats was dissected for proteomic analysis using iTRAQ combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). GO, KEGG pathway, COG, pathways and protein interaction network analyses of the differentially expressed proteins were performed. Several target genes were selected from the proteomic list, and their expression levels in the dorsal raphe nucleus of another 24 mice with identical grouping and treatment using real time real-time quantitative PCR and Western blotting.
RESULTS:A total of 214 differentially expressed proteins were identified in the dorsal raphe nucleus of olanzapine-treated mice, including 72 unregulated and 142 downregulated proteins. GO analyses showed that the differentially expressed proteins were enriched in cellular process, biological regulation, metabolic process, response to stimulus, multicellular organismal process, bindings, catalytic activity, molecular function regulator and transcription regulator activity. KEGG analysis suggested that these proteins were enriched in fluid shear stress and atherosclerosis, serotonergic synapse, butanoate metabolism, thyroid hormone synthesis and IL-17 signaling pathway. The differentially expressed proteins Cav1, Hsp90b1, Canx, Gnai1, MAPK9, and LOC685513 were located at the nodes of the protein-protein interaction network in close relation with metabolic disorders. In olanzapine-treated mice, the expression of Hmgcs2, a negative regulator of apoptosis, was significantly down-regulated in the dorsal raphe nucleus, where the expressions of Pla2g4e, Slc6a4 and Gnai1 involved in serotonergic synapse were significantly upregulated.
CONCLUSION:In the early stage of treatment, olanzapine may contribute to the occurrence of metabolic disorders in rats by regulating the expressions of Cav1, Hsp90b1, Canx, Gnai1, MAPK9, LOC685513 (Gng14) and 5-HTR2 synapse-related proteins in the dorsal raphe nucleus.
