The impact of multifunctional enkephalin analogs and morphine on the protein changes in crude membrane fractions isolated from the rat brain cortex and hippocampus

0583343 - FGÚ 2025 RIV US eng J - Článek v odborném periodiku
Ujčíková, Hana - Lee, Y. S. - Roubalová, Lenka - Svoboda, Petr
The impact of multifunctional enkephalin analogs and morphine on the protein changes in crude membrane fractions isolated from the rat brain cortex and hippocampus.
Peptides. Roč. 174, April (2024), č. článku 171165. ISSN 0196-9781. E-ISSN 1873-5169
Grant CEP: GA MŠMT(CZ) LTAUSA18110
Institucionální podpora: RVO:67985823
Klíčová slova: multifunctional enkephalin analogs * KOR antagonism * morphine * rat brain * crude membrane fractions * proteomic analysis
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 3, rok: 2022
https://doi.org/10.1016/j.peptides.2024.171165

Endogenous opioid peptides serve as potent analgesics through the opioid receptor (OR) activation. However, they often suffer from poor metabolic stability, low lipophilicity, and low blood-brain barrier permeability. Researchers have developed many strategies to overcome the drawbacks of current pain medications and unwanted biological effects produced by the interaction with opioid receptors. Here, we tested multifunctional enkephalin analogs LYS739 (MOR/DOR agonist and KOR partial antagonist) and LYS744 (MOR/DOR agonist and KOR full antagonist) under in vivo conditions in comparison with MOR agonist, morphine. We applied 2D electrophoretic resolution to investigate differences in proteome profiles of crude membrane (CM) fractions isolated from the rat brain cortex and hippocampus exposed to the drugs (10 mg/kg, seven days). Our results have shown that treatment with analog LYS739 induced the most protein changes in cortical and hippocampal samples. The identified proteins were mainly associated with energy metabolism, cell shape and movement, apoptosis, protein folding, regulation of redox homeostasis, and signal transduction. Among these, the isoform of mitochondrial ATP synthase subunit beta (ATP5F1B) was the only protein upregulation in the hippocampus but not in the brain cortex. Contrarily, the administration of analog LYS744 caused a small number of protein alterations in both brain parts. Our results indicate that the KOR full antagonism, together with MOR/DOR agonism of multifunctional opioid ligands, can be beneficial in treating chronic pain states by reducing changes in protein expression levels but retaining analgesic efficacy.
Trvalý link: https://hdl.handle.net/11104/0351315