Excitotoxic and Radiation Stress Increase TERT Levels in the Mitochondria and Cytosol of Cerebellar Purkinje Neurons

• Published in: Cerebellum (London, England) England), 2016-08, Vol.15 (4), p.509-517
• Main Authors: Eitan, Erez, Braverman, Carmel, Tichon, Ailone, Gitler, Daniel, Hutchison, Emmette R., Mattson, Mark P., Priel, Esther
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Nucleus - enzymology; Cell Nucleus - pathology; Cell Nucleus - radiation effects; Cytosol - enzymology; Cytosol - pathology; Cytosol - radiation effects; DNA Damage - physiology; DNA Damage - radiation effects; Electron Transport Complex IV - metabolism; Fluorescent Antibody Technique; Glutamic Acid - toxicity; Immunoblotting; Male; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - enzymology; Mitochondria - pathology; Mitochondria - radiation effects; Neurobiology; Neurology; Neurosciences; Original Paper; Purkinje Cells - enzymology; Purkinje Cells - pathology; Purkinje Cells - radiation effects; Radiation Injuries, Experimental - enzymology; Radiation Injuries, Experimental - pathology; Stress, Physiological - physiology; Stress, Physiological - radiation effects; Telomerase - genetics; Telomerase - metabolism; Tissue Culture Techniques; X-Rays - adverse effects
• ISSN: 1473-4222; 1473-4230
• DOI: 10.1007/s12311-015-0720-6

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, an enzyme that elongates telomeres at the ends of chromosomes during DNA replication. Recently, it was shown that TERT has additional roles in cell survival, mitochondrial function, DNA repair, and Wnt signaling, all of which are unrelated to telomeres. Here, we demonstrate that TERT is enriched in Purkinje neurons, but not in the granule cells of the adult mouse cerebellum. TERT immunoreactivity in Purkinje neurons is present in the nucleus, mitochondria, and cytoplasm. Furthermore, TERT co-localizes with mitochondrial markers, and immunoblot analysis of protein extracts from isolated mitochondria and synaptosomes confirmed TERT localization in mitochondria. TERT expression in Purkinje neurons increased significantly in response to two stressors: a sub-lethal dose of X-ray radiation and exposure to a high glutamate concentration. While X-ray radiation increased TERT levels in the nucleus, glutamate exposure elevated TERT levels in mitochondria. Our findings suggest that in mature Purkinje neurons, TERT is present both in the nucleus and in mitochondria, where it may participate in adaptive responses of the neurons to excitotoxic and radiation stress.