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allied
academies
17
th
International Conference on
4
th
International Conference on
NEUROLOGY AND NEUROSCIENCE
&
MENTAL HEALTH AND PRIMARY CARE
October 16-18, 2017 | Toronto, Canada
J Neurol Neurorehabil Res 2017 | Volume 2 Issue 3
DNA nanoprobe for real-time imaging and simultaneous quantification of mitochondrial Ca
2+
and pH
in neurons induced by superoxide anion and aggregated amyloid beta
Yang Tian
and
Zhichao Liu
East China Normal University, China
M
itochondria play vital roles in cellular energy
production, signal transduction and Ca
2+
homeostasis,
as well as the cell death. Besides, mitochondrial pH and Ca
2+
are closely associated with cellular functions and diseases.
Thus, simultaneous imaging and biosensing are essential
for understanding inter-relationship between Ca
2+
and pH in
physiological and pathological processes. Herein, we created
a highly selective DNA nanoprobe for real-time imaging and
simultaneous quantification of pH and Ca
2+
in mitochondria,
in which a new Ca
2+
fluorescent probe was synthesized and
assembled onto a DNA nanostructure together with pH-
responsive, inner-reference, and mitochondria-targeted
molecules. This new nanoprobe powerfully tracked pH
and Ca
2+
dynamics at the same localization in response
to superoxide anion (O
2•-
)-induced oxidative stress and
aggregated amyloid beta (Aβ) stimulation with a temporal
resolution of milliseconds. Using this new tool, we
discovered that acid-sensing ion channel 1a (ASIC1a) channel
plays a vital role in O
2•--
and Aβ-induced mitochondrial Ca
2+
burst, which may contribute to neuron death. Moreover,
psalmotoxin 1 (PcTX1) effectively protects against neuron
injury, providing a potential drug for O
2•-
and/or Aβ-induced
neuronal death. Using the DNA-assembled nanosensor for
determination of pH and Ca
2+
at the same localization, we
demonstrated that mitochondrial Ca
2+
is increased
~
4-fold in
neurons compared with HeLa cells, whereas mitochondrial
pH exhibits no obvious difference between the two types
of cells. Furthermore, experimental results demonstrated
diverse mitochondrial Ca
2+
and pH values in different
regions of neurons. The close relationship between Ca
2+
and pH in mitochondria was discovered. Mitochondrial pH
value in neurons obviously increased with increasing Ca
2+
concentration, which may be attributed to the function of
the Ca
2+
/H
+
antiporter in mitochondria. On the other hand,
the mitochondrial Ca
2+
burst can be adjusted by the ASIC1a
channel during cytoplasmic acidosis. O2•- induces transitory
cytoplasmic acidosis, which may activate the ASIC1a channel
in the mitochondrial membrane, resulting in alkalization and
Ca
2+
overload in mitochondria. Mitochondrial Ca
2+
overload is
possibly one of the important factors in O
2•--
induced neuronal
death. These results offer a new view for understanding
the signaling pathway of ROS-induced oxidative stress and
neuron injury. Aggregated Aβ is highly toxic to neurons.
After stimulation by Aβ25-35, the pH value in the cytoplasm
clearly decreased together with the Ca
2+
burst, leading to
acidification and Ca
2+
overload in mitochondria through
ASIC1a. PcTX1 protein protect neurons from death by
preventing mitochondrial Ca
2+
overload stimulated by O
2•-
and aggregated Aβ, suggesting that PcTX1 is a potential drug
for O
2•-
and/or Aβ-induced neuronal death.
Speaker Biography
Yang Tian, PhD is a Professor of Analytical Chemistry in East China Normal University.
She received her PhD degree in Electronic Chemistry fromTokyo Institute of Technology.
After a Post-doctoral training at University of Tokyo, she was appointed as a Professor
in the Department of Chemistry at Tongji University, China in 2005. Then, she joined
in East China Normal University as a specifically appointed Professor since 2013.
Her research expertise is molecular imaging, biosensor, and bio-nanotechnology for
understanding neuroscience. She has coauthored over 70 papers and book chapters.
e:
ytian@chem.ecnu.edu.cn