Neuroprotective Signaling Mechanisms of Telomerase Are Regulated by Brain-Derived Neurotrophic Factor in Rat Spinal Cord Motor Neurons

• DOI: 10.1097/nen.0b013e318222b97b
• Publication Date: 2011-06-10T11:57:20Z
• Authors: Chenchen Niu; Henry K. Yip
• Keywords: 0301 basic medicine; 572; Motor Neurons - drug effects; Apoptosis; Nerve Tissue Proteins; Brain-derived neurotrophic factor; Gene Expression Regulation, Enzymologic; Neuronal survival; 03 medical and health sciences; Brain-Derived Neurotrophic Factor - pharmacology; In Situ Nick-End Labeling; Animals; Humans; RNA, Messenger; Spinal cord motor neuron; Enzyme Inhibitors; RNA, Small Interfering; Promoter Regions, Genetic; Telomerase; Telomerase - metabolism; Cells, Cultured; Motor Neurons; Apoptosis - drug effects - physiology; Dose-Response Relationship, Drug; L-Lactate Dehydrogenase; Brain-Derived Neurotrophic Factor; Carbocyanines; Embryo, Mammalian; Caspase 9; Spinal Cord - cytology; Benzimidazoles; Calcium

Telomerase can promote neuron survival and be regulated by growth factors such as brain-derived neurotrophic factor (BDNF). Increases of BDNF expression telomerase activity after brain injury suggest that may involved in BDNF-mediated neuroprotection. We investigated regulation rat spinal cord motor neurons (SMNs). Our results indicate increases levels SMNs activates mitogen-activated protein kinase/extracellular signal-regulated kinases 1 2 phosphatidylinositol-3-OH kinase/protein kinase B signals, their downstream transcription nuclear factor-κB, c-Myc, Sp1. Administration the tyrosine receptor inhibitor K-252a, PD98059, LY294002 abolished BDNF-induced upregulation these expression. The factor-κB Bay11-7082 also attenuated c-Myc Sp1 increased promoter activity. Spinal with higher induced became more resistant to apoptosis; overexpressed catalytic component reverse transcriptase was enhanced against apoptosis. neuronal survival-promoting effect mediated through Bcl-2, Bax, p53, maintenance mitochondrial membrane potential. Taken together, data neuroprotective via is inhibition apoptotic pathways.