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Induction of oxidative stress by long-term treatment of live HEK293 cells with therapeutic concentration of lithium is associated with down-regulation of delta-opioid receptor amount and function

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F18%3A43919492" target="_blank" >RIV/00023752:_____/18:43919492 - isvavai.cz</a>

  • Alternative codes found

    RIV/67985823:_____/18:00492456 RIV/68081715:_____/18:00492456

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/pii/S0006295218302120?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0006295218302120?via%3Dihub</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.bcp.2018.06.004" target="_blank" >10.1016/j.bcp.2018.06.004</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Induction of oxidative stress by long-term treatment of live HEK293 cells with therapeutic concentration of lithium is associated with down-regulation of delta-opioid receptor amount and function

  • Original language description

    The functional state of delta-opioid receptor signaling cascade in live cells exposed to a therapeutic concentration of lithium for a prolonged period of time (weeks) is not known because the previous studies of Li interference with OR were oriented to mu-OR only. The same applies to the analysis of the prolonged effect of Li on oxidative stress in context with delta-OR function. HEK293 cells stably expressing delta-OR were cultivated in the presence or absence of 1 mM LiCl for 7 or 21 days, homogenized and the post-nuclear (PNS) and plasma membrane (PM) fractions prepared from all four types of cells Level of delta-OR in PM was determined by specific radioligand [H-3]DADLE binding and immunoblot assays; the functional coupling between delta-OR and G proteins was determined as DADLE-stimulated high-affinity [S-35]GTP gamma S binding. In the whole cells, general oxidative stress was monitored by fluorescent dye 2&apos;,7&apos;-dichlorofluorescein diacetate (DCF) and results verified by analysis of PNS and isolated PM. Generation of 4-hydroxy-2-nonenal (4-HNE)-protein adducts and malondialdehyde (MDA) level were determined as products of lipid peroxidation. Li-treated cells exhibited the decreased amount of delta-OR. This was evidenced by both [H-3]DADLE binding and immunoblot assays. The delta-OR-G protein coupling efficiency was diminished Simultaneously, in Li-treated cells, the highly increased oxidative stress measured as DCF fluorescence intensity was noticed. Importantly, this result was detected in live cells as well as PNS and PM. Accordingly, production of 4-HNE-protein adducts and MDA was clearly increased in Li-treated cells. The general significance of our work lies in presentation of novel data indicating that prolonged exposure of live HEK293 cells to the therapeutic concentration of Li results in down-regulation of delta-OR protein level and attenuation of delta-OR function in parallel with increased oxidative stress and increased level of lipid peroxidation products.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30104 - Pharmacology and pharmacy

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2018

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Biochemical Pharmacology

  • ISSN

    0006-2952

  • e-ISSN

  • Volume of the periodical

    154

  • Issue of the periodical within the volume

    August

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    12

  • Pages from-to

    452-463

  • UT code for WoS article

    000441369600044

  • EID of the result in the Scopus database

    2-s2.0-85048573684