자료유형  

 학위논문

Control Number  

0016932909

International Standard Book Number  

9798379879525

Dewey Decimal Classification Number  

616

Main Entry-Personal Name  

Grzymkowski, Julia Kinsey.

Publication, Distribution, etc. (Imprint  

[S.l.] : North Carolina State University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(148 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-01, Section: B.

General Note  

Advisor: Nascone-Yoder, Nanette.

Dissertation Note  

Thesis (Ph.D.)--North Carolina State University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약The widely used herbicide atrazine (ATR) has been epidemiologically associated with structural birth defects in multiple organ systems; however, the mechanism by which ATR disrupts organogenesis is unknown. We have found that Xenopusembryos exposed to this environmental toxicant exhibit intestinal malrotation, a common human birth defect. In addition, ATR-exposed intestines are shorter, suggesting that ATR perturbs the process of elongation. Consistent with this idea, immunostaining of ATR-exposed guts revealed abnormalities in cell shape and polarization at early stages, and in cell division at later stages, indicative of a failure to execute the cell rearrangement and proliferation events that together drive intestine elongation. As an herbicide, ATR inhibits the photosynthetic electron transport chain (ETC) in chloroplasts, leading to the overproduction of reactive oxygen species (ROS) in plants. In animal cells, ATR can also elicit oxidative stress and dysregulate metabolism, and both cell polarization and division are energy-dependent processes, suggesting that ATR-induced intestinal defects may be a result of ETC inhibition in mitochondria. Indeed, ATR exposure increased total levels of ROS within the embryo. Moreover, RNA sequencing analysis of control and ATR exposed intestines revealed an enrichment for genes involved in cell migration, cell cycle regulation, and metabolism, and inhibition of mitochondrial metabolism independent of ATR phenocopied the defects seen after ATR exposure. Finally, metabolomic profile analyses revealed changes in TCA cycle/glycolysis metabolites after ATR exposure, and biochemical flux analyses revealed changes in metabolic pathway usage normally over time and after ATR exposure. Our results reveal a potentially novel mechanism of action of ATR on intestinal development and suggest that metabolic dysfunction may underlie the etiology of a common birth defect.

Subject Added Entry-Topical Term  

Cancer.

Subject Added Entry-Topical Term  

Birth defects.

Subject Added Entry-Topical Term  

Pollutants.

Subject Added Entry-Topical Term  

Toxicity.

Subject Added Entry-Topical Term  

Biosynthesis.

Subject Added Entry-Topical Term  

Mitochondria.

Subject Added Entry-Topical Term  

Energy.

Subject Added Entry-Topical Term  

Metabolism.

Subject Added Entry-Topical Term  

Apoptosis.

Subject Added Entry-Topical Term  

Cell cycle.

Subject Added Entry-Topical Term  

Cell culture.

Subject Added Entry-Topical Term  

Asymmetry.

Subject Added Entry-Topical Term  

Oxidative stress.

Subject Added Entry-Topical Term  

Herbicides.

Subject Added Entry-Topical Term  

Cell adhesion & migration.

Subject Added Entry-Topical Term  

Carbon.

Subject Added Entry-Topical Term  

Pesticides.

Subject Added Entry-Topical Term  

Cardiomyocytes.

Subject Added Entry-Topical Term  

Cyclin-dependent kinases.

Subject Added Entry-Topical Term  

Phosphorylation.

Subject Added Entry-Topical Term  

Enzymes.

Subject Added Entry-Topical Term  

Metabolites.

Subject Added Entry-Topical Term  

Agricultural chemistry.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Chemistry.

Subject Added Entry-Topical Term  

Organic chemistry.

Subject Added Entry-Topical Term  

Toxicology.

Added Entry-Corporate Name  

North Carolina State University.

Host Item Entry  

Dissertations Abstracts International. 85-01B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643639