Hyperglycemic Conditions Affect Shape and Ca2+ Homeostasis of Mitochondria in Endothelial Cells
- 1 October 2004
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Cardiovascular Pharmacology
- Vol. 44 (4), 423-436
- https://doi.org/10.1097/01.fjc.0000139449.64337.1b
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.Keywords
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