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Paltauf-Doburzynska, J; Malli, R; Graier, WF.
Hyperglycemic conditions affect shape and Ca2+ homeostasis of mitochondria in endothelial cells.
J CARDIOVASC PHARMACOL. 2004; 44(4): 423-436.
Doi: 10.1097%2F01.fjc.0000139449.64337.1b
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- Leading authors Med Uni Graz
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Graier Wolfgang
- Co-authors Med Uni Graz
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Malli Roland
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- Abstract:
- In this study the contribution of alternating architecture and Ca2+ handling of mitochondria to cytosolic Ca2+ homeostasis was elucidated under normoglycemic and hyperglycemic (HGC) conditions in the human endothelial cell line EA.hy926. Exposure of endothelial cells to hyperglycemic medium elevated basal cytosolic free Ca2+ concentration ([Ca2+]cyto), the histamine-initiated cytosolic Ca2+ signaling, and the mitochondrial Ca2+ content after cell stimulation. The latter was possibly due to the prolonged mitochondrial Ca2+ elevation in response to agonists found in HGC-pretreated cells. Moreover, under HGC mitochondrial free radical production was increased and mitochondrial shape changed from a mainly tubular, highly interconnected network toward multiple, isolated singular structures. Such changes could not be correlated with HGC-induced alterations of cytosolic Ca2+ signaling that became normalized with antimycin A, an inhibitor of the respiratory chain. These data suggest that although mitochondrial structure changes considerably during HGC, alterations in cytosolic Ca2+ signaling are more likely due to the enhanced energy status/metabolism of the mitochondria. On the other hand, in normoglycemic cells of unforced fragmentation of mitochondria yielded elevated basal [Ca2+]cyto, while the global Ca2+ signaling in response to histamine remained unchanged. Thus, mitochondrial architecture (ie, tubular versus fragmented structure) per se does not have a detectable impact on agonist-initiated global cytosolic Ca2+ signaling, while this organelle represents an early target in hyperglycemia leading to alterations in cytosolic Ca2+ signaling.
- Find related publications in this database (using NLM MeSH Indexing)
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Calcium - metabolism
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Calcium Signaling - metabolism
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Cell Line - metabolism
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Cytosol - metabolism
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Endothelial Cells - ultrastructure
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Endothelium, Vascular - ultrastructure
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Free Radicals - metabolism
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Homeostasis - metabolism
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Humans - metabolism
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Hyperglycemia - pathology
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Mitochondria - metabolism
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Signal Transduction - metabolism
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Time Factors - metabolism
- Find related publications in this database (Keywords)
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endothelial Ca2+
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mitochondrial Ca2+ homeostasis
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diabetes
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histamine
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ratiometric pericam-mt