Molecular imaging of labile iron(II) pools in living cells with a turn-on fluorescent probe.
Iron is an essential metal for living organisms, but misregulation of its homeostasis at the cellular level can trigger detrimental oxidative and/or nitrosative stress and damage events. Motivated to help study the physiological and pathological consequences of biological iron regulation, we now report a reaction-based strategy for monitoring labile Fe(2+) pools in aqueous solution and living cells. Iron Probe 1 (IP1) exploits a bioinspired, iron-mediated oxidative C-O bond cleavage reaction to achieve a selective turn-on response to Fe(2+) over a range of cellular metal ions in their bioavailable forms. We show that this first-generation chemical tool for fluorescence Fe(2+) detection can visualize changes in exchangeable iron stores in living cells upon iron supplementation or depletion, including labile iron pools at endogenous, basal levels. Moreover, IP1 can be used to identify reversible expansion of labile iron pools by stimulation with vitamin C or the iron regulatory hormone hepcidin, providing a starting point for further investigations of iron signaling and stress events in living systems as well as future probe development.
Departments of Chemistry and ‡Molecular and Cell Biology and §Howard Hughes Medical Institute, University of California , Berkeley, California 94720, United States.
Ho Yu
HY
Au-Yeung
Jefferson
J
Chan
Teera
T
Chantarojsiri
Christopher J
CJ
Chang
D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival; D015195:Drug Design; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D056945:Hep G2 Cells; D064451:Hepcidins / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D057054:Molecular Imaging / Q000379:methods*
D005456:Fluorescent Dyes; D064451:Hepcidins; D007501:Iron; D001205:Ascorbic Acid