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    Vectors of transmission: An early nicotine puff triggers a long-lasting microRNA molecular “memory” in C. elegans.

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    Author
    Taki, Faten
    Abstract
    The prevalence of passive and active nicotine exposure among neonates, children and adolescents remains relatively high and varies among cultures and countries. Currently, there is ample evidence that a safe nicotine dose or level does not exist. For that, early exposure to any nicotine product is considered "catastrophic" to the children's future and wellbeing. The cycle of nicotine addiction, relapse, and enduring health disparities remains unpreventable. This is majorly due to the incomplete understanding of nicotine-induced molecular signaling and mechanisms. Recently, the role of epigenetics in the developmental origin of diseases has been highlighted. With this in mind, this study aims to identify and validate the roles of particular epigenetics factors known as microRNAs in nicotine-induced early and late-onset diseases. Our workflow started with post-embryonic exposure to nicotine and was followed by global microRNA profiling across three generations. Based on the transcriptomic findings, we identified 14 transgenerational miRNAs that can serve as biomarkers for early parental nicotine exposure. Bioinformatics analysis coupled with a literature review allowed us to focus on three factors: mpk-1, sir-2.1, miR-80 for further validation. We were intrigued in finding a potential relationship among these factors (MS80) in mediating nicotine induced early and late-onset diseases. For that, we performed reverse genetics assays and tested their contribution to nicotine-induced larval developmental delay, larval pharyngeal pumping inhibition, adult reproduction, adult mean lifespan, and adult germ line apoptosis. Our results showed that nicotine delayed development in an MS80 independent manner. Meanwhile, MS80 had a role in mediating nicotine-induced pharyngeal pumping inhibition. As for nicotine enduring effects, our data showed that post-embryonic nicotine exposure delayed the onset of reproduction without impacting fertility. This early exposure also had a negative effect on mean worm lifespan which was promoted by nicotine-induced upregulation of miR-80. In addition, our data also allowed us to infer that early nicotine exposure increases the ROS levels which trigger an organism level response that is mediated by MS80 to induce adult germ line apoptosis. Our study is the first to show the role of MS80 in intra and transgenerational inheritance of nicotine-induced effects. We also identified functional human homologs for cel-miR-80 in nicotine addiction and discussed the promising potential of manipulating MS80 to counteract nicotine-induced cellular and organismal damage during the early stages. Therefore, MS80 could be used as a prevention approach for nicotine-induced late-onset diseases.
    URI
    http://hdl.handle.net/10342/5884
    Subject
     neonates; post-embryonic; adults; developmental delay; neuromotor function; pharyngeal pumping; reproduction; lifespan; germ line apoptosis; MAPK; sirtuins; miR-80 
    Date
    2016-06-16
    Citation:
    APA:
    Taki, Faten. (June 2016). Vectors of transmission: An early nicotine puff triggers a long-lasting microRNA molecular “memory” in C. elegans. (Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/5884.)

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    MLA:
    Taki, Faten. Vectors of transmission: An early nicotine puff triggers a long-lasting microRNA molecular “memory” in C. elegans.. Doctoral Dissertation. East Carolina University, June 2016. The Scholarship. http://hdl.handle.net/10342/5884. August 07, 2022.
    Chicago:
    Taki, Faten, “Vectors of transmission: An early nicotine puff triggers a long-lasting microRNA molecular “memory” in C. elegans.” (Doctoral Dissertation., East Carolina University, June 2016).
    AMA:
    Taki, Faten. Vectors of transmission: An early nicotine puff triggers a long-lasting microRNA molecular “memory” in C. elegans. [Doctoral Dissertation]. Greenville, NC: East Carolina University; June 2016.
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    • Biology
    • Dissertations
    Publisher
    East Carolina University

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