Targeting glutathione with the triterpenoid CDDO-Im protects against benzo-a-pyrene-1,6-quinone-induced cytotoxicity in endothelial cells

Epidemiological studies have exhibited a strong correlation between exposure to air pollution and deaths due to vascular diseases such as atherosclerosis. Benzo-a-pyrene-1,6-quinone (BP-1,6-Q) is one of the components of air pollution . This study was to examine the role of GSH in BP-1,6-Q mediated...

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Published in:Molecular and cellular biochemistry 2020-11, Vol.474 (1-2), p.27-39
Main Authors: Shukla, Halley, Lee, Ho Young, Koucheki, Ashkon, Bibi, Humaira A., Gaje, Gabriella, Sun, Xiaolun, Zhu, Hong, Li, Y. Robert, Jia, Zhenquan
Format: Article
Language:English
Subjects:
Air pollution
Analysis
Apoptosis
Atherosclerosis
Benzopyrenes - adverse effects
Biochemistry
Biomedical and Life Sciences
Blood circulation disorders
Cardiology
Cells, Cultured
Cytoprotection
Development and progression
Endothelium
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Epidemiology
Glutathione - metabolism
Humans
Imidazoles - pharmacology
Life Sciences
Lipid Peroxidation
Medical Biochemistry
Necrosis
Oleanolic Acid - analogs & derivatives
Oleanolic Acid - pharmacology
Oncology
Protective Agents - pharmacology
Quinone
Reactive Oxygen Species - metabolism
Thiobarbituric Acid Reactive Substances - metabolism
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Summary:Epidemiological studies have exhibited a strong correlation between exposure to air pollution and deaths due to vascular diseases such as atherosclerosis. Benzo-a-pyrene-1,6-quinone (BP-1,6-Q) is one of the components of air pollution . This study was to examine the role of GSH in BP-1,6-Q mediated cytotoxicity in human EA.hy96 endothelial cells and demonstrated that induction of cellular glutathione by a potent triterpenoid, CDDO-Im (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole), protects cells against BP-1,6-Q induced protein and lipid damage. Incubation of EA.hy926 endothelial cells with BP-1,6-Q caused a significant increase in dose-dependent cytotoxicity as measured by LDH release assay and both apoptotic and necrotic cell deaths as measured by flow cytometric analysis. Incubation of EA.hy926 endothelial cells with BP-1,6-Q also caused a significant decrease in cellular GSH levels. The diminishment of cellular GSH by buthionine sulfoximine (BSO) potentiated BP-1,6-Q-induced toxicity significantly suggesting a critical involvement of GSH in BP-1,6-Q induced cellular toxicity. GSH-induction by CDDO-Im significantly protects cells against BP-1,6-Q induced protein and lipid damage as measured by protein carbonyl (PC) assay and thiobarbituric acid reactive substances (TBARS) assay, respectively. However, the co-treatment of cells with CDDO-Im and BSO reversed the cytoprotective effect of CDDO-Im on BP-1,6-Q-mediated lipid peroxidation and protein oxidation. These results suggest that induction of GSH by CDDO-Im might be the important cellular defense against BP-1,6-Q induced protein and lipid damage. These findings would contribute to better understand the action of BP-1,6-Q and may help to develop novel therapies to protect against BP-1,6-Q-induced atherogenesis.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-020-03831-6