Schnegelberger, Regina
(2021)
STRUCTURAL AND FUNCTIONAL DISRUPTION OF MITOCHONDRIAL HOMEOSTASIS BY THE ENVIRONMENTAL TOXICANT VINYL CHLORIDE.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Vinyl chloride (VC) is an environmental toxicant that directly causes liver injury at high concentrations. However, lower concentrations (< OSHA limits), which are not overtly hepatotoxic, enhance injury caused by high-fat diet (HFD), at least in part, via mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondria and the ER closely interact via mitochondria-associated membranes (MAMs). Alterations in these contact sites are associated with mitochondrial dysfunction and ER stress. The purpose of this study was to investigate the impact of VC exposure on the damage, function and interaction (via MAMs) of these organelles. C57Bl/6J mice, fed HFD, or low-fat control diet (LFD), were exposed to VC (<1 ppm), or room air for 6 hrs/d, 5 d/wk for up to 12 wks. Alpha mouse liver 12 (AML12) cells were exposed to the VC metabolite, chloroacetaldehyde (CAA) for 20 hrs at 37°C. VC exposure modified mitochondrial morphology by increasing mitochondrial area, independent of diet while mitochondrial DNA content was unaffected. VC also decreased levels of key MAM complex proteins. CAA exposure increased mitochondrial size and altered the proximity between the ER and mitochondria in AML12 cells. Taken together, VC and CAA altered mitochondrial structure and organelle interactions. These stress responses may be causal in VC-mediated toxicity and sensitization. These data highlight that current safety restrictions may be insufficient to address VC-induced hepatotoxicity in humans.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Schnegelberger, Regina | rds88@pitt.edu | rds88 | |
|
| ETD Committee: |
|
| Date: |
10 September 2021 |
| Date Type: |
Publication |
| Defense Date: |
4 August 2021 |
| Approval Date: |
10 September 2021 |
| Submission Date: |
17 August 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
53 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Pharmacology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Mitochondria, Hepatotoxicity, Environmental, Toxicant, Vinyl Chloride, Mechanism |
| Date Deposited: |
10 Sep 2021 19:25 |
| Last Modified: |
10 Sep 2021 19:25 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41774 |
Available Versions of this Item
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}