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SHR Neuro Krebs Kardio Lipid

Charoensin, S; Eroglu, E; Opelt, M; Bischof, H; Madreiter-Sokolowski, CT; Kirsch, A; Depaoli, MR; Frank, S; Schrammel, A; Mayer, B; Waldeck-Weiermair, M; Graier, WF; Malli, R.
Intact mitochondrial Ca2+ uniport is essential for agonist-induced activation of endothelial nitric oxide synthase (eNOS).
Free Radic Biol Med. 2017; 102(1):248-259 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Bischof Helmut
Depaoli Maria Rosa
Eroglu Emrah
Frank Saša
Graier Wolfgang
Kirsch Andrijana
Madreiter-Sokolowski Corina
Malli Roland
Waldeck-Weiermair Markus

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Number of Figures: 7
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Mitochondrial Ca2+ uptake regulates diverse endothelial cell functions and has also been related to nitric oxide (NO) production. However, it is not entirely clear if the organelles support or counteract NO biosynthesis by taking up Ca2+. The objective of this study was to verify whether or not mitochondrial Ca2+ uptake influences Ca2+-triggered NO generation by endothelial NO synthase (eNOS) in an immortalized endothelial cell line (EA.hy926), respective primary human umbilical vein endothelial cells (HUVECs) and eNOS-RFP (red fluorescent protein) expressing human embryonic kidney (HEK293) cells. We used novel genetically encoded fluorescent NO probes, the geNOps, and Ca2+ sensors to monitor single cell NO and Ca2+ dynamics upon cell treatment with ATP, an inositol 1,4,5-trisphosphate (IP3)-generating agonist. Mitochondrial Ca2+ uptake was specifically manipulated by siRNA-mediated knock-down of recently identified key components of the mitochondrial Ca2+ uniporter machinery. In endothelial cells and the eNOS-RFP expressing HEK293 cells we show that reduced mitochondrial Ca2+ uptake upon the knock-down of the mitochondrial calcium uniporter (MCU) protein and the essential MCU regulator (EMRE) yield considerable attenuation of the Ca2+-triggered NO increase independently of global cytosolic Ca2+ signals. The knock-down of mitochondrial calcium uptake 1 (MICU1), a gatekeeper of the MCU, increased both mitochondrial Ca2+ sequestration and Ca2+-induced NO signals. The positive correlation between mitochondrial Ca2+ elevation and NO production was independent of eNOS phosphorylation at serine1177. Our findings emphasize that manipulating mitochondrial Ca2+ uptake may represent a novel strategy to control eNOS-mediated NO production. Copyright © 2016. Published by Elsevier Inc.
Find related publications in this database (using NLM MeSH Indexing)
Calcium - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Endothelial Cells - enzymology
HEK293 Cells -
HeLa Cells -
Human Umbilical Vein Endothelial Cells -
Humans -
Membrane Potential, Mitochondrial -
Mitochondria - enzymology
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - genetics
Nitric Oxide Synthase Type III - metabolism
Phosphorylation -
Signal Transduction -

Find related publications in this database (Keywords)
Endothelial nitric oxide production
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