Morphine is one of the most effective and widely used analgesics in medicine. However, it is also known for its neuroprotective and cardioprotective effects in ischemic disease. The detailed molecular mechanism of these protective effects is still unknown. Current research on the protective effects of morphine is now focusing on mitochondrial ATP-sensitive potassium channels (mKATPs). Activators of mKATP channels have protective effects on cells. There is evidence that morphine can activate these mKATP channels through the activation of opioid receptors. This signaling pathway may therefore be part of the protective effects of morphine. The signaling cascade from opioid channel activation to modulation of mKATP channel activity has not yet been described. The proposed links in the signaling cascade responsible for mKATP activation are intramitochondrial protein kinase Cε (PKCε) and cytosolic protein kinase G (PKG). This project aims to determine the involvement of mKATP in morphine preconditioning. In particular, the project focuses on mitochondrial function and activation of anti-apoptotic and proapoptotic signaling pathways. Morphine preconditioning is induced in the model neuroblastoma cell line SH -SY5Y by chronic exposure to morphine. Cellular damage due to oxidative stress will be mimicked by the addition of tert-butyl hydroperoxide. The obtained results may be useful for understanding the mechanisms of morphine preconditioning and morphine-induced neuroprotection.

 

Five relevant publications of the research group:

  1. Melkes B., Hejnova L. and Novotny J. (2016) Biased μ-opioid receptor agonists diversely regulate lateral mobility and functional coupling of the receptor to its cognate G proteins. Naunyn-Schmiedeberg´s Arch. Pharmacol. 389:1289-1300.
  2. Skrabalova J, Karlovska I, Hejnova L, Novotny J. Protective Effect of Morphine Against the Oxidant-Induced Injury in H9c2 Cells. Cardiovasc Toxicol. 2018;18(4):374-85.
  3. Markova V, Hejnova L, Benda A, Novotny J, Melkes B. β-Arrestin 1 and 2 similarly influence μ-opioid receptor mobility and distinctly modulate adenylyl cyclase activity Cell Signal. 2021, 87,110124
  4. Drastichova Z, Hejnova L, Moravcova R, Novotny J. Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine. Life. 2021, 11(7), 683
  5. Ujcikova H, Hejnova L, Eckhardt A, Roubalova L, Novotny J, Svoboda P. Impact of three-month morphine withdrawal on rat brain cortex, hippocampus, striatum and cerebellum: proteomic and phosphoproteomic studies. Neurochem Int. 2021, 144, 104975
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