1 research outputs found
Magnetic Resonance Imaging of Mitochondrial Dysfunction and Metabolic Activity, Accompanied by Overproduction of Superoxide
This study shows that a mitochondria-penetrating
nitroxide probe
(mito-TEMPO) allows detection of superoxide and visualization of mitochondrial
dysfunction in living cells due to the effect of <i>T</i><sub>1</sub> shortening in MRI. Mitochondrial dysfunction was induced
by treatment of cells with rotenone and 2-methoxyestradiol (2-ME/Rot).
The MRI measurements were performed on 7T MRI. The 2-ME/Rot-treated
cells were characterized by overproduction of superoxide, which was
confirmed by a conventional dihydroethidium test. In the presence
of mito-TEMPO, the intensity of MRI signal in 2-ME/Rot-treated cells
was ∼30–40% higher, in comparison with that in untreated
cells or culture media. In model (cell-free) systems, we observed
that superoxide, but not hydrogen peroxide, increased the intensity
of <i>T</i><sub>1</sub>-weighted MRI signal of mito-TEMPO.
Moreover, the superoxide restores the <i>T</i><sub>1</sub>-weighted MRI contrast of mito-TEMPOH, a noncontrast (diamagnetic)
analogue of mito-TEMPO. This was also confirmed by using EPR spectroscopy.
The results demonstrate that superoxide radical is involved in the
enhancement of <i>T</i><sub>1</sub>-weighted MRI contrast
in living cells, in the absence and presence of mito-TEMPO. This report
gives a direction for discovering new opportunities for functional
MRI, for detection of metabolic activity, accompanied by overproduction
of superoxide, as well as by disturbance of the balance between superoxide
and hydrogen peroxide, a very important approach to clarify the fine
molecular mechanisms in the regulation of many pathologies. The visualization
of mitochondrial activity in real-time can be crucial to clarify the
molecular mechanism of the functional MRI in its commonly accepted
definition, as a method for detection of neurovascular coupling