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Medientyp:
E-Artikel
Titel:
Polyunsaturated fatty acids mobilize intracellular Ca2+ in NT2 human teratocarcinoma cells by causing release of Ca2+ from mitochondria
Beteiligte:
Zhang, Bin-Xian;
Ma, Xiuye;
Zhang, Wanke;
Yeh, Chih-Ko;
Lin, Alan;
Luo, Jian;
Sprague, Eugene A.;
Swerdlow, Russell H.;
Katz, Michael S.
Erschienen:
American Physiological Society, 2006
Erschienen in:
American Journal of Physiology-Cell Physiology, 290 (2006) 5, Seite C1321-C1333
Sprache:
Englisch
DOI:
10.1152/ajpcell.00335.2005
ISSN:
0363-6143;
1522-1563
Entstehung:
Anmerkungen:
Beschreibung:
In a variety of disorders, overaccumulation of lipid in nonadipose tissues, including the heart, skeletal muscle, kidney, and liver, is associated with deterioration of normal organ function, and is accompanied by excessive plasma and cellular levels of free fatty acids (FA). Increased concentrations of FA may lead to defects in mitochondrial function found in diverse diseases. One of the most important regulators of mitochondrial function is mitochondrial Ca2+ ([Ca2+]m), which fluctuates in coordination with intracellular Ca2+ ([Ca2+]i). Polyunsaturated FA (PUFA) have been shown to cause [Ca2+]i mobilization albeit by unknown mechanisms. We have found that PUFA but not monounsaturated or saturated FA cause [Ca2+]i mobilization in NT2 human teratocarcinoma cells. Unlike the [Ca2+]i response to the muscarinic G protein-coupled receptor agonist carbachol, PUFA-mediated [Ca2+]i mobilization in NT2 cells is independent of phospholipase C and inositol-1,4,5-trisphospate (IP3) receptor activation, as well as IP3-sensitive internal Ca2+ stores. Furthermore, PUFA-mediated [Ca2+]i mobilization is inhibited by the mitochondria uncoupler carboxyl cyanide m-chlorophenylhydrozone. Direct measurements of [Ca2+]m with X-rhod-1 and 45Ca2+ indicate that PUFA induce Ca2+ efflux from mitochondria. Further studies show that ruthenium red, an inhibitor of the mitochondrial Ca2+ uniporter, blocks PUFA-induced Ca2+ efflux from mitochondria, whereas inhibitors of the mitochondrial permeability transition pore cyclosporin A and bongkrekic acid have no effect. Thus PUFA-gated Ca2+ release from mitochondria, possibly via the Ca2+ uniporter, appears to be the underlying mechanism for PUFA-induced [Ca2+]i mobilization in NT2 cells.