Mitochondrial DNA-depleted neuroblastoma (Rho degrees) cells exhibit altered calcium signaling

Citation
Tb. Sherer et al., Mitochondrial DNA-depleted neuroblastoma (Rho degrees) cells exhibit altered calcium signaling, BBA-MOL CEL, 1496(2-3), 2000, pp. 341-355
Citations number
44
Categorie Soggetti
Cell & Developmental Biology
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
ISSN journal
01674889 → ACNP
Volume
1496
Issue
2-3
Year of publication
2000
Pages
341 - 355
Database
ISI
SICI code
0167-4889(20000417)1496:2-3<341:MDN(DC>2.0.ZU;2-H
Abstract
To investigate the role of chronic mitochondrial dysfunction on intracellul ar calcium signaling, we studied basal and stimulated cytosolic calcium lev els in SH-SY5Y cells and a derived cell line devoid of mitochondrial DNA (R ho degrees). Basal cytosolic calcium levels were slightly but significantly reduced in Rho degrees cells, The impact of chronic depletion of mitochond rial DNA was more evident following exposure of cells to carbachol, a calci um mobilizing agent. Calcium transients generated in Rho degrees cells foll owing application of carbachol were more rapid than those in SH-SY5Y cells. A plateau phase of calcium recovery during calcium transients was present in SH-SY5Y cells but absent in Rho degrees cells. The rapid calcium transie nts in Rho degrees cells were due, in part, to increased reliance on Na+/Ca 2+ exchange activity at the plasma membrane and the plateau phase in calciu m recovery in SH-SY5Y cells was dependent on the presence of extracellular calcium. We also examined whether mitochondrial DNA depletion influenced ca lcium responses to release of intracellular calcium stores. Rho degrees cel ls showed reduced responses to the uncoupler, FCCP, and the sarcoplasmic re ticulum calcium ATPase inhibitor, thapsigargin. Acute exposure of SH-SY5Y c ells to mitochondrial inhibitors did not mimic the results seen in Rho degr ees cells, These results suggest that cytosolic calcium homeostasis in this neuron-like cell line is significantly altered as a consequence of chronic depletion of mitochondrial DNA. (C) 2000 Elsevier Science B.V. All rights reserved.