October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
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- Past Research Festivals
Zidovudine (AZT) promotes hepatic lipid accumulation through increased oxidative and endoplasmic reticulum stress
| Thursday, November 07, 2013 — Poster Session II | |||
|---|---|---|---|
12:00 p.m. – 2:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIAAA |
PHARM-3 |
Authors
- A Banerjee
- M.A. Abdelmegeed
- S Jang
- B.J. Song
Abstract
The clinical effectiveness of Zidovudine (AZT) is constrained due to its side-effects including hepatic steatosis and toxicity. However, the mechanism of hepatic lipid accumulation in AZT-treated individuals is unknown. We hypothesized that AZT-mediated oxidative and endoplasmic reticulum (ER) stress may increase the fat synthesis and suppress the fat metabolizing enzymes, leading to fat accumulation. AZT treatment of C57BL/6J female mice (400 mg/day/kg body weight, i.p) for 10 consecutive days significantly increased hepatic triglyceride levels, inflammation and toxicity. Markers of oxidative stress such as protein oxidation, nitration, glycation and lipid peroxidation were significantly higher in the AZT-treated mice compared to the corresponding vehicle controls. Further, the levels of ER stress marker proteins like GRP78, p-PERK, and p-eIF2α were significantly elevated in AZT-treated mice. The level of nuclear SREBP-1c, a transcription factor involved in fat synthesis, was increased while significantly decreased protein levels of acetyl-CoA carboxylase, phospho-AMP kinase and PPARα as well as inactivation of 3-keto-acyl-CoA thiolase in the mitochondrial β-oxidation pathway were observed in AZT-exposed mice compared to those in control animals. Collectively, these data suggest that elevated oxidative and ER stress plays a key role, at least partially, in lipid accumulation, inflammation and hepatotoxicity in AZT-treated mice.
