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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
Zhichao Liu
and
Yang Tian
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
Zhichao Liu, PhD is a student of Analytical Chemistry under the supervision of Prof.
Tian in East China Normal University. He received his MS degree in Analytical Chemistry
from Nanchang University in 2015. His doctoral research now focuses on the design,
synthesis, characterization, and application of fluorescent nanomaterial for sensing
and imaging in biological applications.
e:
liuzhichao582@sina.com