Premium
Intracellular Zinc Elevation Measured with a “Calcium‐Specific” indicator: A Question on Calcium Signals
Author(s) -
Li Yang V,
Stork Christian J,
Wu Shiyong
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1351-a
Subject(s) - calcium , zinc , chemistry , thapsigargin , fura 2 , fluorescence , calcium in biology , intracellular , divalent , biophysics , chelation , cytosol , biochemistry , inorganic chemistry , biology , organic chemistry , enzyme , physics , quantum mechanics
Much of our current evidence concerning of the role of calcium (Ca2+) or Ca2+ signaling comes from fluorescent studies with so‐called “calcium indicators.” However, many of those same Ca2+ indicators have a higher affinity for divalent cation zinc (Zn2+) than for Ca2+. Here, we investigated metal‐ion responses by screening nominally Ca2+‐selective fluorophores in solutions containing various concentrations of Zn2+. Ca2+‐sensitive dyes such as Calcium Green‐1, Fura‐2, and Fluo‐3 showed a wide range of interaction with Zn2+, even responding to Zn2+ in the presence of high concentrations of Ca2+, demonstrating that these fluorescent Ca2+ indicators can be used effectively to measure dynamic changes of cytosolic Zn2+in situ. We then investigated the rising Zn2+ transients in neurons during ischemia simulated by oxygen and glucose deprivation (OGD) which caused a marked rise in intracellular zinc. Next we used the calcium probe, Calcium Green‐1, to determine whether calcium, like zinc, also rises intracellularly. The Calcium Green‐1 fluorescence did in fact rise dramatically, but chelation of zinc (and not Ca2+) by TPEN dramatically reversed that increased fluorescence, suggesting that rising zinc, not rising Ca2+, is the primary source of the increasing calcium‐green fluorescence. Finally, zinc chelation gave a substantial reduction in the number of “dying” neurons, and also reduced thapsigargin induced “Ca2+” transient. Therefore, re‐evaluation of the role of intracellular calcium in neuronal injury is warranted. Supports: the American Heart Association (Y.V.L) and the National Institutes of Health (Y.V.L)