Protection of the Crayfish Mechanoreceptor Neuron and Glial Cells from Photooxidative Injury by Modulators of Diverse Signal Transduction Pathways

Abstract

Oxidative stress is the reason of diverse neuropathological processes. Photodynamic therapy (PDT), an effective inducer of oxidative stress, is used for cancer treatment, including brain tumors. We studied the role of various signaling pathways in photodynamic injury and protection of single neurons and satellite glial cells in the isolated crayfish mechanoreceptor. It was photosensitized with alumophthalocyanine Photosens in the presence of inhibitors or activators of various signaling proteins. PDT eliminated neuronal activity and killed neurons and glial cells. Inhibitory analysis showed the involvement of protein kinases Akt, glycogen synthase kinase-3β (GSK-3β), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), calmodulin, calmodulin-dependent kinase II (CaMKII), adenylate cyclase, and nuclear factor NF-κB in PDT-induced necrosis of neurons. Nitric oxide (NO) and glial cell-derived neurotrophic factor (GDNF) reduced neuronal necrosis. In glial cells, protein kinases Akt, calmodulin, and CaMKII; protein kinases C and G, adenylate cyclase, and p38; and nuclear transcription factor NF-κB also mediated PDT-induced necrosis. In contrast, NO and neurotrophic factors nerve growth factor (NGF) and GDNF demonstrated anti-necrotic activity. Phospholipase Cγ, protein kinase C, GSK-3β, mTOR, NF-κB, mitochondrial permeability transition pores, and NO synthase mediated PDT-induced apoptosis of glial cells, whereas protein kinase A, tyrosine phosphatases, and neurotrophic factors NGF, GDNF, and neurturin were involved in protecting glial cells from photoinduced apoptosis. Signaling pathways that control cell survival and death differed in neurons and glia. Inhibitors or activators of some signaling pathways may be used as potential protectors of neurons and glia from photooxidative stress and following death.

Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders

“…Cortical neurons can be protected by BDNF through the induction of autophagy and the inhibition of mTOR during oxygen deprivation . In other scenarios, glial cell‐derived neurotrophic factor (GDNF) and nerve growth factor (NGF) protect against photo‐oxidative stress with inhibition of mTOR activity . The concentrations of growth factors also may affect mTOR signalling and apoptotic cell death.…”

Immediate Release of Gastrin-Releasing Peptide Mediates Delayed Radiation-Induced Pulmonary Fibrosis

“…44 Because we observe several phosphoprotein changes, we propose that several of these, especially focal adhesion kinase signaling [identified in the Ingenuity Pathway Analysis (Qiagen Bioinformatics, Redwood City, CA)] and NF-kB activation, are likely to be direct effects of high-affinity GRP receptor and/or lower-affinity neuromedin B receptor activation. Deficient protein kinase A signaling in RT þ PBS versus sham þ PBS lung could promote acute lung injury during early radiation pneumonitis and/or RTPF 45 because protein kinase A activation can protect against oxidative stresseinduced lung injury and fibrosis. 46 In contrast, we observed distinct changes in phosphoproteins and signaling in RT þ mAb 2A11 versus RT þ PBS lungs.…”

Photodynamic therapy-induced nitric oxide production in neuronal and glial cells

“…However, it played the proapoptotic rather than antiapoptotic role. 9 On the other hand, NO produced in the glial envelope could protect neurons from PDTinduced necrosis and impairment of neuronal activity. 7…”

“…It has been used as a simple but informative experimental model in the studies of signaling mechanisms of photodynamic effect on neurons and glial cells. 4,[7][8][9] Nitric oxide (NO) is a second messenger, involved in the regulation of various cellular functions. It participates in neurotransmission, cell responses to stress, and neurodegeneration.…”