Mercury specifically induces LINE-1 activity in a human neuroblastoma cell line.
L1 retro-elements comprise 17% of the human genome. Approximately 100 copies of these autonomous mobile elements are active in our DNA and can cause mutations, gene disruptions, and genomic instability. Therefore, human cells control the activities of L1 elements, in order to prevent their deleterious effects through different mechanisms. However, some toxic agents increase the retrotransposition activity of L1 elements in somatic cells. In order to identify specific effects of neurotoxic metals on L1 activity in neuronal cells, we studied the effects of mercury and cobalt on L1-retroelement activity by measuring levels of cellular transcription, protein expression, and genomic retrotransposition in a neuroblastoma cell line compared with the effects in three non-neuronal cell lines. Our results show that mercury increased the expression of L1 RNA, the activity of the L1 5'UTR, and L1 retrotransposition exclusively in the neuroblastoma cell line but not in non-neuronal cell lines. However, cobalt increased the expression of L1 RNA in neuroblastoma cells, HeLa cells, and wild-type human fibroblasts, and also increased the activity of the L1 5'UTR as well as the SV40 promoter in HeLa cells but not in neuroblastoma cells. Exposure to cobalt did not result in increased retrotransposition activity in HeLa cells or neuroblastoma cells. We conclude that non-toxic levels of the neurotoxic agent mercury could influence DNA by increasing L1 activities, specifically in neuronal cells, and may make these cells susceptible to neurodegeneration over time.
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Laleh
L
Habibi
Iranian National Cell Bank, Pasteur Institute of Iran, Iran. Electronic address: mashokrgozar@pasteur.ac.ir.
Mohammad Ali
MA
Shokrgozar
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mina
M
Tabrizi
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Hossein
MH
Modarressi
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: akramism@tums.ac.ir.
Seyed Mohammad
SM
Akrami
D020121:5' Untranslated Regions; D045744:Cell Line, Tumor; D003035:Cobalt / Q000633:toxicity; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects*; D008628:Mercury / Q000633:toxicity*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018626:Retroelements; D013539:Simian virus 40 / Q000235:genetics
D020121:5' Untranslated Regions; D018626:Retroelements; D003035:Cobalt; D008628:Mercury
Cobalt; L1 retrotransposition; Mercury; Neuron