| 11045967 |
Kimura C, Oike M, Ito Y: Hypoxia-induced alterations in Ca (2+) mobilization in brain microvascular endothelial cells. Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2310-8.
To investigate the possible cellular mechanisms of the ischemia-induced impairments of cerebral microcirculation, we investigated the effects of hypoxia/reoxygenation on the intracellular Ca (2+) concentration ([Ca (2+)](i)) in bovine brain microvascular endothelial cells (BBEC). In the cells kept in normal air, ATP elicited Ca (2+) oscillations in a concentration-dependent manner. When the cells were exposed to hypoxia for 6 h and subsequent reoxygenation for 45 min, the basal level of [Ca (2+)](i) was increased from 32.4 to 63.3 nM, and ATP did not induce Ca (2+) oscillations. Hypoxia/reoxygenation also inhibited capacitative Ca (2+) entry (CCE), which was evoked by thapsigargin (Delta [Ca (2+)](i-CCE): control, 62.3 +/- 3.1 nM; hypoxia/reoxygenation, 17.0 +/- 1.8 nM). The impairments of Ca (2+) oscillations and CCE, but not basal [Ca (2+)](i), were restored by superoxide dismutase and the inhibitors of mitochondrial electron transport, rotenone and thenoyltrifluoroacetone (TTFA). By using a superoxide anion (O (2)(-))-sensitive luciferin derivative MCLA, we confirmed that the production of O (2)(-) was induced by hypoxia/reoxygenation and was prevented by rotenone and TTFA. These results indicate that hypoxia/reoxygenation generates O (2)(-) at mitochondria and impairs some Ca (2+) mobilizing properties in BBEC. |
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