Polyunsaturated fatty acids mobilize intracellular Ca 2+ in NT2 human teratocarcinoma cells by causing release of Ca 2+ from mitochondria

Bin Xian Zhang, Xiuye Ma, Wanke Zhang, Chih Ko Yeh, Alan Lin, Jian Luo, Eugene A. Sprague, Russell H. Swerdlow, Michael S. Katz

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 Ca 2+ ([Ca 2+] m), which fluctuates in coordination with intracellular Ca 2+ ([Ca 2+] i). Polyunsaturated FA (PUFA) have been shown to cause [Ca 2+] i mobilization albeit by unknown mechanisms. We have found that PUFA but not monounsaturated or saturated FA cause [Ca 2+] i mobilization in NT2 human teratocarcinoma cells. Unlike the [Ca 2+] i response to the muscarinic G protein-coupled receptor agonist carbachol, PUFA-mediated [Ca 2+] i mobilization in NT2 cells is independent of phospholipase C and inositol-1,4,5-trisphospate (IP 3) receptor activation, as well as IP 3-sensitive internal Ca 2+ stores. Furthermore, PUFA-mediated [Ca 2+] i mobilization is inhibited by the mitochondria uncoupler carboxyl cyanide m-chlorophenylhydrozone. Direct measurements of [Ca 2+] m with X-rhod-1 and 45Ca 2+ indicate that PUFA induce Ca 2+ efflux from mitochondria. Further studies show that ruthenium red, an inhibitor of the mitochondrial Ca 2+ uniporter, blocks PUFA-induced Ca 2+ efflux from mitochondria, whereas inhibitors of the mitochondrial permeability transition pore cyclosporin A and bongkrekic acid have no effect. Thus PUFA-gated Ca 2+ release from mitochondria, possibly via the Ca 2+ uniporter, appears to be the underlying mechanism for PUFA-induced [Ca 2+] i mobilization in NT2 cells.

Original languageEnglish (US)
Pages (from-to)C1321-C1333
JournalAmerican Journal of Physiology - Cell Physiology
Volume290
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Arachidonic acid
  • G protein-coupled receptor
  • IP receptor
  • Mitochondrial Ca uniporter

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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