Photodynamic therapy based on photogeneration of cytotoxic singlet oxygen and following oxidative stress is currently used in neuro-oncology for destruction of brain tumors.However,along with a tumor,it damages health...Photodynamic therapy based on photogeneration of cytotoxic singlet oxygen and following oxidative stress is currently used in neuro-oncology for destruction of brain tumors.However,along with a tumor,it damages healthy neurons and glial cells.We studied the involvement of the glutamate-related signaling pathway in photodynamic damage to normal glial cells in the crayfish stretch receptor.This model object consists of a single neuron surrounded by glial cells.It was photosensitized with alumophthalocyanine Photosens and irradiated by the diode laser(670 nm).Application of enzyme inhibitors and ion channels modulators showed that exogenous L-glutamate decreased photoinduced apoptosis of crayfish glial cells.The natural neuroglial mediator N-acetylaspartylglutamate,which releases glutamate after splitting by glutamate carboxypeptidase II,also inhibited photoinduced apoptosis.Inhibition of glutamate carboxypeptidase II,oppositely,enhanced glial apoptosis.This confirmed the antiapoptotic activity of glutamate.Glutamate agonist NMDA or inhibitor of NMDA receptors MK801 did not influence photodynamic death of glial cells,i.e.,these receptors did not participate in glial apoptosis.Inhibition of metabotropic glutamate receptors mGluRI with AP-3 reduced PDT-induced apoptosis of glial cells.Thus,chemical modifiers of various signaling processes can modulate photoinduced necrosis or apoptosis of glial cells and thus modify efficiency of photodynamic therapy.展开更多
基金The work was supported by the grants of the Russian Foundation for Basic Research No.05-04048440 and 08-04-01322 and the grant No.2.1.1/6185 of the Ministry of Education and Science of Russian Federation.
文摘Photodynamic therapy based on photogeneration of cytotoxic singlet oxygen and following oxidative stress is currently used in neuro-oncology for destruction of brain tumors.However,along with a tumor,it damages healthy neurons and glial cells.We studied the involvement of the glutamate-related signaling pathway in photodynamic damage to normal glial cells in the crayfish stretch receptor.This model object consists of a single neuron surrounded by glial cells.It was photosensitized with alumophthalocyanine Photosens and irradiated by the diode laser(670 nm).Application of enzyme inhibitors and ion channels modulators showed that exogenous L-glutamate decreased photoinduced apoptosis of crayfish glial cells.The natural neuroglial mediator N-acetylaspartylglutamate,which releases glutamate after splitting by glutamate carboxypeptidase II,also inhibited photoinduced apoptosis.Inhibition of glutamate carboxypeptidase II,oppositely,enhanced glial apoptosis.This confirmed the antiapoptotic activity of glutamate.Glutamate agonist NMDA or inhibitor of NMDA receptors MK801 did not influence photodynamic death of glial cells,i.e.,these receptors did not participate in glial apoptosis.Inhibition of metabotropic glutamate receptors mGluRI with AP-3 reduced PDT-induced apoptosis of glial cells.Thus,chemical modifiers of various signaling processes can modulate photoinduced necrosis or apoptosis of glial cells and thus modify efficiency of photodynamic therapy.
