Journal
ACS NANO
Volume 12, Issue 12, Pages 12357-12368Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b06322
Keywords
DNA nanoprobe; mitochondria; calcium; pH; neuron imaging; real-time
Categories
Funding
- NSFC [21635003, 21325521]
- Program of Shanghai Subject Chief Scientist [15XD1501600]
- Innovation Program of Shanghai Municipal Education Commission [201701070005E00020]
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Herein, a single highly selective DNA nanoprobe was designed and created for the real-time imaging and simultaneous quantification of two kinds of biological species using Ca2+ and pH; the molecules were selected as models because of their close relationship with cellular functions and diseases. A Ca2+ fluorescent probe was synthesized and assembled onto a DNA nanostructure together with pH-responsive, inner-reference, and mitochondria-targeted molecules. This nanoprobe with high spatial resolution, together with long-term fluorescent and structural stability, powerfully tracked pH and Ca2+ dynamics at the same localization in mitochondria in response to O-2(center dot-)-induced oxidative stress and aggregated amyloid beta (A beta) stimulation with a temporal resolution of milliseconds. Using this tool, we discovered that O-2(center dot-) and A beta triggered transitory cytoplasmic acidosis and then activated acid-sensing ion channel la (ASIC1a) in the mitochondrial membrane, leading to mitochondrial Ca2+ overload and pH abnormalities, which contribute to neuron death. Moreover, psalmotoxin 1 effectively protected against O-2(center dot-) - and A beta-induced neuron injury.
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