PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD

Sinthia Alam; Gwendolyn S Carter; Kimberly J Krager; Xueshu Li; Hans-Joachim Lehmler; Nukhet Aykin-Burns

doi:10.3390/antiox7090121

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PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD

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PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD

Sinthia Alam, Gwendolyn S Carter, Kimberly J Krager, Xueshu Li, Hans-Joachim Lehmler and Nukhet Aykin-Burns

Antioxidants, Vol.7(9), p.121

09/15/2018

DOI: 10.3390/antiox7090121

PMCID: PMC6162768

PMID: 30223548

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Abstract

Although the production of polychlorinated biphenyls (PCBs) is prohibited, the inadvertent production of certain lower-chlorinated PCB congeners still threatens human health. We and others have identified 3,3'-dichlorobiphenyl (PCB11) and its metabolite, 3,3'-dichlorobiphenyl-4-ol (4OH-PCB11), in human blood, and there is a correlation between exposure to this metabolite and mitochondrial oxidative stress in mammalian cells. Here, we evaluated the downstream effects of 4OH-PCB11 on mitochondrial metabolism and function in the presence and absence of functional Sirtuin 3 (SIRT3), a mitochondrial fidelity protein that protects redox homeostasis. A 24 h exposure to 3 μM 4OH-PCB11 significantly decreased the cellular growth and mitochondrial membrane potential of SIRT3-knockout mouse embryonic fibroblasts (MEFs). Only wild-type cells demonstrated an increase in Manganese superoxide dismutase (MnSOD) activity in response to 4OH-PCB11⁻induced oxidative injury. This suggests the presence of a SIRT3-mediated post-translational modification to MnSOD, which was impaired in SIRT3-knockout MEFs, which counters the PCB insult. We found that 4OH-PCB11 increased mitochondrial respiration and endogenous fatty-acid oxidation-associated oxygen consumption in SIRT3-knockout MEFs; this appeared to occur because the cells exhausted their reserve respiratory capacity. To determine whether these changes in mitochondrial respiration were accompanied by similar changes in the regulation of fatty acid metabolism, we performed quantitative real-time polymerase chain reaction (qRT-PCR) after a 24 h treatment with 4OH-PCB11. In SIRT3-knockout MEFs, 4OH-PCB11 significantly increased the expression of ten genes controlling fatty acid biosynthesis, metabolism, and transport. When we overexpressed MnSOD in these cells, the expression of six of these genes returned to the baseline level, suggesting that the protective role of SIRT3 against 4OH-PCB11 is partially governed by MnSOD activity.

PCB 11

Sirtuin 3

4OH-PCB11

fatty acid metabolism

mitochondria

MnSOD

ISRP Project 1 2015-2020

Synthesis Core

Details

Title: Subtitle: PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD
Creators: Sinthia Alam - Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. SAlam2@uams.edu
Gwendolyn S Carter - Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Gwendolyn.Carter@np.edu
Kimberly J Krager - Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. KJKrager@uams.edu
Xueshu Li - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA. xueshu-li@uiowa.edu
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA. hans-joachim-lehmler@uiowa.edu
Nukhet Aykin-Burns - Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. NAykinBurns@uams.edu
Resource Type: Journal article
Publication Details: Antioxidants, Vol.7(9), p.121
DOI: 10.3390/antiox7090121
PMID: 30223548
PMCID: PMC6162768
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Publisher: Switzerland
Grant note: P20 GM109005 / National Institute of General Medical Sciences P30 ES005605 / NIEHS NIH HHS P20 GM109005 / NIGMS NIH HHS P42 ES013661 / National Institute of Environmental Health Sciences P42 ES013661 / NIEHS NIH HHS R15 ES022781 / NIEHS NIH HHS R15 ES022781 / National Institute of Environmental Health Sciences
Language: English
Date published: 09/15/2018
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Iowa Superfund Research Program
Record Identifier: 9984001085502771

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