Cartiotonic steroids affect monolayer permeability in lymphatic endothelial cells.

Szczegóły
Abstrakt

Tytuł:: Cartiotonic steroids affect monolayer permeability in lymphatic endothelial cells.
Autorzy:: Horvat D; Orion Institute for Translational Medicine, Temple, TX, USA.; Emergent Biotechnologies LLC, Temple, TX, USA.
Afroze SH; Orion Institute for Translational Medicine, Temple, TX, USA.; Emergent Biotechnologies LLC, Temple, TX, USA.
Cromer WE; Department of Medical Physiology, Texas A&M Health Science Center College of Medicine, Bryan, TX, USA.
Pantho AF; Orion Institute for Translational Medicine, Temple, TX, USA.; Emergent Biotechnologies LLC, Temple, TX, USA.
Ashraf AHMZ; Baylor Scott and White Health Medical Center, Temple, TX, USA.
Kuehl TJ; Orion Institute for Translational Medicine, Temple, TX, USA.; Emergent Biotechnologies LLC, Temple, TX, USA.
Zawieja DC; Department of Medical Physiology, Texas A&M Health Science Center College of Medicine, Bryan, TX, USA.
Uddin MN; Orion Institute for Translational Medicine, Temple, TX, USA. .; Emergent Biotechnologies LLC, Temple, TX, USA. .; Department of Medical Physiology, Texas A&M Health Science Center College of Medicine, Bryan, TX, USA. .
Źródło:: Molecular and cellular biochemistry [Mol Cell Biochem] 2021 Aug; Vol. 476 (8), pp. 3207-3213. Date of Electronic Publication: 2021 Apr 18.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: New York : Springer
Original Publication: The Hague, Dr. W. Junk B. V. Publishers.
MeSH Terms:: Cell Membrane Permeability*
Bufanolides/*pharmacology
Endothelial Cells/*pathology
Gene Expression Regulation/*drug effects
Nitric Oxide/*metabolism
Vasoconstrictor Agents/*pharmacology
Animals ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Phosphorylation ; Rats
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Contributed Indexing:: Keywords: Cardiotonic steroids; Lymphatic endothelial cells permeability; Preeclampsia; Tight junctions
Substance Nomenclature:: 0 (Bufanolides)
0 (Vasoconstrictor Agents)
31C4KY9ESH (Nitric Oxide)
3KBT25GV2B (marinobufagenin)
Entry Date(s):: Date Created: 20210418 Date Completed: 20210906 Latest Revision: 20210906
Update Code:: 20240104
DOI:: 10.1007/s11010-021-04147-9
PMID:: 33866492
: Czasopismo naukowe

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Edema is common in preeclampsia (preE), a hypertensive disorder of pregnancy. Cardiotonic steroids (CTSs) such as marinobufagenin (MBG) are involved in the pathogenesis of preE. To assess whether CTSs are involved in the leakage of lymphatic endothelial cell (LEC), we evaluated their effect on monolayer permeability of LECs (MPLEC) in culture. A rat mesenteric LECs were treated with DMSO (vehicle), and CTSs (MBG, CINO, OUB) at concentrations of 1, 10, and 100 nM. Some LECs were pretreated with 1 μM L-NAME (N-Nitro-L-Arginine Methyl Ester) before adding 100 nM MBG or cinobufotalin (CINO). Expression of β-catenin and vascular endothelial (VE)-cadherin in CTS-treated LECs was measured by immunofluorescence and MPLEC was quantified using a fluorescence plate reader. Western blot was performed to measure β-catenin and VE-cadherin protein levels and myosin light chain 20 (MLC20) phosphorylation. MBG (≥ 1 nM) and CINO (≥ 10 nM) caused an increase (p < 0.05) in the MPLEC compared to DMSO while ouabain (OUB) had no effect. Pretreatment of LECs with 1 μM L-NAME attenuated (p < 0.05) the MPLEC. The β-catenin expression in LECs was downregulated (p < 0.05) by MBG and CINO. However, there was no effect on the LECs tight junctions for the CINO group. VE-cadherin expression was downregulated (p < 0.05) by CINO, and MLC20 phosphorylation was upregulated (p < 0.05) by MBG. We demonstrated that MBG and CINO caused an increase in the MPLEC, which were attenuated by L-NAME pretreatment. The data suggest that CTSs exert their effect via nitric-oxide-dependent signaling pathway and may be involved in vascular leak syndrome of LEC lining in preE.

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