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Endoplasmic reticulum Ca 2+ signaling and mitochondrial Cyt c release in astrocytes following oxygen and glucose deprivation
Author(s) -
Liu Yan,
Kintner Douglas B.,
Begum Gulnaz,
Algharabli Jehad,
Cengiz Pelin,
Shull Gary E.,
Liu XiangJun,
Sun Dandan
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06862.x
Subject(s) - endoplasmic reticulum , cytosol , mitochondrion , unfolded protein response , cytochrome c , chemistry , biology , biochemistry , microbiology and biotechnology , endocrinology , medicine , enzyme
J. Neurochem. (2010) 114 , 1436–1446. Abstract In the present study, we investigated changes of cytosolic Ca 2+ ([Ca 2+ ] cyt ), endoplasmic reticulum Ca 2+ ([Ca 2+ ] ER ) and mitochondrial Ca 2+ (Ca 2+ m ) in astrocytes following oxygen/glucose deprivation and reoxygenation (OGD/REOX). Two hours OGD did not cause changes in [Ca 2+ ] cyt , but led to a significant increase in [Ca 2+ ] ER . The elevation in [Ca 2+ ] ER continued and reached a peak level (130 ± 2 μM) by 90 min REOX. An abrupt release of Ca 2+ ER occurred during 1.5–2.5 h REOX, which was accompanied with a delayed and sustained rise in [Ca 2+ ] cyt . Moreover, Ca 2+ m content was increased significantly within 15 min REOX followed by a secondary rise (∼4.5‐fold) and a release of mitochondrial cytochrome c (Cyt c ). Astrocytes exhibited translocation of Cyt c from mitochondria to endoplasmic reticulum (ER) and up regulation of ER stress protein p‐eIF2α. Blocking Na + ‐K + ‐Cl − cotransporter isoform 1 activity, either by its potent inhibitor bumetanide or genetic ablation, abolished release of ER Ca 2+ , delayed rise in [Ca 2+ ] cyt and Ca 2+ m . Inhibition of the reverse mode operation of the Na + /Ca 2+ exchanger significantly attenuated OGD/REOX‐mediated Cyt c release. In summary, this study illustrates that OGD/REOX triggers a time‐dependent loss of Ca 2+ homeostasis in cytosol and organelles (ER and mitochondria) in astrocytes. Collective stimulation of Na + ‐K + ‐Cl − cotransporter isoform 1 and reverse mode function of Na + /Ca 2+ exchanger contributes to these changes.