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Hypoxic remodeling of Ca2+ stores in type I cortical astrocytes.
J Biol Chem 2003; 278(7):4875-81JB

Abstract

Prolonged periods of hypoxia are deleterious to higher brain functions and increase the likelihood of developing dementias. Here, we have used fluorimetric techniques to investigate the effects of chronic hypoxia (2.5% O(2), 24 h) on Ca(2+) stores in type I cortical astrocytes, because such stores are crucial to various astrocyte functions, including Ca(2+)-dependent modulation of neuronal activity. Rises of [Ca(2+)](i) evoked by exposure of astrocytes to bradykinin were enhanced following chronic hypoxia, as were transient increases in [Ca(2+)](i) recorded in Ca(2+)-free perfusate. The enhanced responses were due partly to impaired plasmalemmal Na(+)/Ca(2+) exchange following chronic hypoxia. More importantly, chronic hypoxia increased the Ca(2+) content of mitochondria (as determined by exposing cells to mitochondrial inhibitors), such that they were unable to act as Ca(2+) buffers following bradykinin-evoked Ca(2+) release from the endoplasmic reticulum. Hypoxic enhancement of mitochondrial Ca(2+) content was also observed in confocal images of cells loaded with the mitochondrial Ca(2+) indicator, Rhod-2. Confocal imaging of cells loaded with tetramethylrhodamine ethyl ester, an indicator of mitochondrial membrane potential, indicated that mitochondria were hyperpolarized in astrocytes following chronic hypoxia. Our findings indicate that hypoxia disturbs Ca(2+) signaling in type I astrocytes, primarily by causing mitochondrial Ca(2+) overload.

Authors+Show Affiliations

Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12477727

Citation

Smith, Ian F., et al. "Hypoxic Remodeling of Ca2+ Stores in Type I Cortical Astrocytes." The Journal of Biological Chemistry, vol. 278, no. 7, 2003, pp. 4875-81.
Smith IF, Boyle JP, Plant LD, et al. Hypoxic remodeling of Ca2+ stores in type I cortical astrocytes. J Biol Chem. 2003;278(7):4875-81.
Smith, I. F., Boyle, J. P., Plant, L. D., Pearson, H. A., & Peers, C. (2003). Hypoxic remodeling of Ca2+ stores in type I cortical astrocytes. The Journal of Biological Chemistry, 278(7), pp. 4875-81.
Smith IF, et al. Hypoxic Remodeling of Ca2+ Stores in Type I Cortical Astrocytes. J Biol Chem. 2003 Feb 14;278(7):4875-81. PubMed PMID: 12477727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypoxic remodeling of Ca2+ stores in type I cortical astrocytes. AU - Smith,Ian F, AU - Boyle,John P, AU - Plant,Leigh D, AU - Pearson,Hugh A, AU - Peers,Chris, Y1 - 2002/12/10/ PY - 2002/12/13/pubmed PY - 2003/5/6/medline PY - 2002/12/13/entrez SP - 4875 EP - 81 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 278 IS - 7 N2 - Prolonged periods of hypoxia are deleterious to higher brain functions and increase the likelihood of developing dementias. Here, we have used fluorimetric techniques to investigate the effects of chronic hypoxia (2.5% O(2), 24 h) on Ca(2+) stores in type I cortical astrocytes, because such stores are crucial to various astrocyte functions, including Ca(2+)-dependent modulation of neuronal activity. Rises of [Ca(2+)](i) evoked by exposure of astrocytes to bradykinin were enhanced following chronic hypoxia, as were transient increases in [Ca(2+)](i) recorded in Ca(2+)-free perfusate. The enhanced responses were due partly to impaired plasmalemmal Na(+)/Ca(2+) exchange following chronic hypoxia. More importantly, chronic hypoxia increased the Ca(2+) content of mitochondria (as determined by exposing cells to mitochondrial inhibitors), such that they were unable to act as Ca(2+) buffers following bradykinin-evoked Ca(2+) release from the endoplasmic reticulum. Hypoxic enhancement of mitochondrial Ca(2+) content was also observed in confocal images of cells loaded with the mitochondrial Ca(2+) indicator, Rhod-2. Confocal imaging of cells loaded with tetramethylrhodamine ethyl ester, an indicator of mitochondrial membrane potential, indicated that mitochondria were hyperpolarized in astrocytes following chronic hypoxia. Our findings indicate that hypoxia disturbs Ca(2+) signaling in type I astrocytes, primarily by causing mitochondrial Ca(2+) overload. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12477727/Hypoxic_remodeling_of_Ca2+_stores_in_type_I_cortical_astrocytes_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=12477727 DB - PRIME DP - Unbound Medicine ER -