Conjugated linoleic acid improves endothelial Ca2+ signaling by blocking growth factor and cytokine-mediated Cx43 phosphorylation. (15th June 2020)

• Record Type: Journal Article
• Authors: Mauro, Amanda K.; Berdahl, Danielle M.; Khurshid, Nauman; Clemente, Luca; Ampey, Amanda C.; Shah, Dinesh M.; Bird, Ian M.; Boeldt, Derek S.
• Is Part Of: Molecular and cellular endocrinology. Volume 510(2020)
• Publication Date: 2020-06-15
• Subjects: Ca2+ -- Conjugated linoleic acid -- Cytokine -- Growth factor -- Preeclampsia; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2020.110814
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Sustained Ca 2+ burst signaling is crucial for endothelial vasodilator production and is disrupted by growth factors and cytokines. Conjugated linoleic acid (CLA), a Src inhibitor in certain preparations, is generally regarded as safe during pregnancy by the FDA. Multiple CLA preparations; t10, c12 or c9, t11 CLA, or a 1:1 mixture of the two were administered before growth factor or cytokine treatment. Growth factors and cytokines caused a significant decrease in Ca 2+ burst numbers in response to ATP stimulation. Both t10, c12 CLA and the 1:1 mixture rescued VEGF165 or TNFα inhibited Ca 2+ bursts and correlated with Src-specific phosphorylation of connexin 43. VEGF165, TNFα, and IL-6 in combination at physiologic concentrations revealed IL-6 amplified the inhibitory effects of lower dose of VEGF165 and TNFα. Again, the 1:1 CLA mixture was most effective at rescue of function. Therefore, CLA formulations may be a promising treatment for endothelial dysfunction in diseases such as preeclampsia. Highlights: GF/Cyt, alone or in combination, promote endothelial dysfunction and are rescued by the nutraceutical CLA. GF/Cyt coupled directly to Src mediate this damage, and is rescued by t10, c12 CLA or a 1:1 mix of c9, t11 and t10, c12 CLA. Interleukins are less damaging than GFs, and are more resistant to CLA rescue.