Null allele mutants of trt-1, the catalytic subunit of telomerase in Caenorhabditis elegans, are less sensitive to Mn-induced toxicity and DAergic degeneration

• Published in: Neurotoxicology (Park Forest South) Vol. 57; pp. 54 - 60
• Main Authors: Ijomone, Omamuyovwi M., Miah, Mahfuzur R., Peres, Tanara V., Nwoha, Polycarp U., Aschner, Michael
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2016; Elsevier BV
• Subjects: Animals; Animals, Genetically Modified; C. elegans; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Catalysis; Chemotaxis; Chlorides - toxicity; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; DAergic degeneration; Degeneration; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA damage; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine receptors; Dose-Response Relationship, Drug; Environmental risk; Fluorescence; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Green fluorescent protein; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Health risks; Lethality; Locomotion - drug effects; Locomotion - genetics; Manganese; Manganese Compounds; Movement disorders; Mutants; Mutation; Mutation - genetics; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - chemically induced; Neurodegenerative Diseases - mortality; Neurotoxicity; Oxidative stress; Parkinson's disease; Risk factors; RNA-directed DNA polymerase; Sodium chloride; Survival; Survival Analysis; Telomerase; Telomerase - genetics; Telomerase reverse transcriptase; Toxicity; trt-1; Tyrosine 3-Monooxygenase - metabolism; trt-1; C. elegans; Telomerase; DAergic degeneration; Manganese
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2016.08.016

•Telomerase reverse transcriptase (trt-1) is the catalytic subunit of telomerase in Caenorhabditis elegans (C. elegans).•Manganese affects survival of C. elegans and compromises integrity of the dopaminergic (DAergic) system in wt worms.•Null allele mutation in trt-1 does not exacerbate Mn-induced toxicity, but improves survival, and attenuates injury to the DAergic system. Exposure to manganese (Mn) represents an environmental risk factor for Parkinson’s disease (PD). Recent evidence suggests that telomerase reverse transcriptase (TERT), the catalytic subunit of mammalian telomerase participates in non-telomeric functions and may play a role in cellular protection from oxidative stress and DNA damage. trt-1 is the catalytic subunit of telomerase in Caenorhabditis elegans (C. elegans). The present study investigated the relationship between trt-1 mutation and Mn-induced neurotoxicity. Wild-type (wt) and trt-1 worms were subjected to an acute Mn treatment of 1h at the first larval (L1) stage. Survival assay and behavior (Basal slowing response, chemotaxis) were assessed. Dopaminergic (DAergic) neurodegeneration was evaluated in successful crosses of trt-1 worms expressing green fluorescent protein (GFP) (dat-1:GFP worms). trt-1 worms were less sensitive to Mn-induced lethality compared to wt worms. Mn induced DAergic degeneration in wt worms, but not in trt-1 worms. Basal slowing was altered in both wt and trt-1 worms; however trt-1 worms were significantly less affected in their basal slowing behavior compared to wt worms. Mn treatment did not affect chemotaxis by NaCl in either wt or trt-1 mutants worms. Combined, the results establish that null mutation in trt-1 improves survival and attenuates damage to the DAergic system.