Null allele mutants of trt-1, the catalytic subunit of telomerase in Caenorhabditis elegans, are less sensitive to Mn-induced toxicity and DAergic degeneration.
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.
Department of Anatomy, Faculty of Basic Medical Sciences, Cross River University of Technology, Okuku Campus, Cross River, Nigeria; Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, USA; Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Osun, Nigeria.
Omamuyovwi M
OM
Ijomone
Department of Neuroscience, Albert Einstein College of Medicine, New York, USA.
Mahfuzur R
MR
Miah
Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, USA.
Tanara V
TV
Peres
Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Osun, Nigeria.
Polycarp U
PU
Nwoha
Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, USA; Department of Neuroscience, Albert Einstein College of Medicine, New York, USA. Electronic address: Michael.Aschner@einstein.yu.edu.
Michael
M
Aschner
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D017895:Manganese Compounds; D009154:Mutation / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000401:mortality; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002712:Chlorides; C532156:DAT-1 protein, C elegans; D050483:Dopamine Plasma Membrane Transport Proteins; D017895:Manganese Compounds; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D019098:Telomerase; C025340:manganese chloride; D004298:Dopamine
C. elegans; DAergic degeneration; Manganese; Telomerase; trt-1