Kovaleva V.D., Berezhnaya E.V., Rudkovskii M.V., Uzdensky A.B., Department of Biophysics and Biocybernetics, Southern Federal University, Rostov-on-Don, 344090, Russia
The involvement of NO-mediated signaling in PDT-induced death of neurons and glial cells
Kovaleva V.D., Berezhnaya E.V., Rudkovskii M.V., Uzdensky A.B.
Department of Biophysics and Biocybernetics, Southern Federal University, Rostov-on-Don, 344090, Russia
Photodynamic therapy (PDT) is currently used in oncology, particularly, in treatment of brain tumors. We studied the possible role of NO-mediated signaling in photodynamic injury and protection of neurons and surrounding glial cells (GC). Crayfish stretch receptor consisting of a single neuron enveloped by GC was photosensitized with alumophthalocyanine Photosens (50 nM, 30 min incubation) and irradiated with laser diode (670 nm, 0.4 W/cm2). Application of NO generators 10 M sodium nitroprusside and 10 M NONOate, reduced PDT-induced necrosis of GC and showed the same tendency to decrease neuronal necrosis. These compounds did not influence significantly PDT-induced apoptosis of glial cells. Inhibitor of neuronal NO-synthase L-NAME (1mM) significantly increased the percent of PDT-induced necrotic glial cells but did not influence neuronal necrosis. This confirmed the anti-necrotic effect of NO on glial cells and involvement of neuronal NO synthase in protection of glial cells. 1 mM L-NAME, 1 mM L-NNA, another inhibitor of neuronal NO-synthase, as well as 50 μM S-Methhylisothioharnstoff Sulfat (SMT), inhibitor of inducible NO synthase protected glial cells from PDT-induced apoptosis. Therefore, NO may be involved in PDT-induced apoptosis of glial cells. Inhibition of NO-activated protein kinase G with 10 μM KT5823 decreased the percent of necrotic neurons but not glial cells. Therefore, protein kinase G was involved in PDT-induced necrosis of GC, possibly independently on NO. KT5823 also increased the level of GC apoptosis indicating the anti-apoptotic role of protein kinase G. Thus NO is involved in regulation of PDT-induced necrosis of neurons and glial cells as well as in apoptosis of glial cells.
Keywords: NO, photodynamic effect, neuron, glia, cell death
Mrs. Vera Dmitryevna Kovaleva
Southern Federal University, Researcher
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