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The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus, Comparison with Changes Induced by Morphine
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SYSNO ASEP 0560744 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus, Comparison with Changes Induced by Morphine Author(s) Ujčíková, Hana (FGU-C) RID, ORCID
Roubalová, Lenka (FGU-C) RID, ORCID, SAI
Lee, Y. S. (US)
Slaninová, Jiřina (FGU-C)
Brejchová, Jana (FGU-C) RID, ORCID
Svoboda, Petr (FGU-C) RID, ORCIDArticle number 1969 Source Title Biomedicines. - : MDPI
Roč. 10, č. 8 (2022)Number of pages 22 s. Language eng - English Country CH - Switzerland Keywords multifunctional enkephalin analogs ; morphine ; chronic pain treatment ; rat brain ; rat spleen lymphocytes ; proteomic analysis ; label-free quantification OECD category Biochemistry and molecular biology R&D Projects LTAUSA18110 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000846080800001 EID SCOPUS 85137318833 DOI 10.3390/biomedicines10081969 Annotation This work aimed to test the effect of 7-day exposure of rats to multifunctional enkephalin analogs LYS739 and LYS744 at doses of 3 mg/kg and 10 mg/kg on the protein composition of rat spleen lymphocytes, brain cortex, and hippocampus. Alterations of proteome induced by LYS739 and LYS744 were compared with those elicited by morphine. The changes in rat proteome profiles were analyzed by label-free quantification (MaxLFQ). Proteomic analysis indicated that the treatment with 3 mg/kg of LYS744 caused significant alterations in protein expression levels in spleen lymphocytes (45), rat brain cortex (31), and hippocampus (42). The identified proteins were primarily involved in RNA processing and the regulation of cytoskeletal dynamics. In spleen lymphocytes, the administration of the higher 10 mg/kg dose of both enkephalin analogs caused major, extensive modifications in protein expression levels: LYS739 (119) and LYS744 (182). Among these changes, the number of proteins associated with immune responses and apoptotic processes was increased. LYS739 treatment resulted in the highest number of alterations in the rat brain cortex (152) and hippocampus (45). The altered proteins were functionally related to the regulation of transcription and cytoskeletal reorganization, which plays an essential role in neuronal plasticity. Administration with LYS744 did not increase the number of altered proteins in the brain cortex (26) and hippocampus (26). Our findings demonstrate that the effect of kappa-OR full antagonism of LYS744 is opposite in the central nervous system and the peripheral region (spleen lymphocytes). Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://www.mdpi.com/2227-9059/10/8/1969
Number of the records: 1