TNF-alpha Inhibits Pregnancy-adapted Ca Signaling in Uterine Artery Endothelial Cells

Overview

Journal Mol Cell Endocrinol

Specialties Cell Biology
Endocrinology
Molecular Biology

Date 2019 Feb 20

PMID 30779937

Citations 10

Authors

Amanda C Ampey

Derek S Boeldt

Luca Clemente

Mary A Grummer

FuXian Yi

Ronald R Magness

Ian M Bird

Affiliations

Soon will be listed here.

Abstract

Enhancement of vasodilation of uterine arteries during pregnancy occurs through increased connexin (Cx)43 gap junction (GJ) communication supporting more frequent and sustained Ca 'bursts'. Such adaptation is lacking in subjects with preeclampsia (PE). Here we show TNF-alpha, commonly increased in PE subjects, inhibits Cx43 function and Ca bursts in pregnancy-derived ovine uterine artery endothelial cells (P-UAEC) via Src and MEK/ERK phosphorylation of Cx43, and this can be reversed by PP2 or U0126. Of relevance to humans: (1) the nutraceutical Src antagonist t10, c12 CLA also recovers Ca bursting in P-UAEC. (2) TNF-alpha can reduce and PP2 rescue Ca bursting and NO output in human umbilical vein endothelium (HUV Endo) preparations. (3) Treatment of HUV Endo from PE subjects with PP2 alone can rescue bursting and NO output. We conclude TNF-alpha acts via Src more than MEK/ERK to inhibit GJ Cx43 function in PE subjects, and CLA may offer a potential therapy.

Citing Articles

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Src kinase partially mediates cytokine-induced endothelial dysfunction.

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