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

Authors

Halley Shukla, Department of Biology, The University of North Carolina At Greensboro, 312 Eberhart Building, 321 McIver Street, Greensboro, NC, 27402-6170, USA.
Ho Young Lee, Department of Biology, The University of North Carolina At Greensboro, 312 Eberhart Building, 321 McIver Street, Greensboro, NC, 27402-6170, USA.
Ashkon Koucheki, Department of Biology, The University of North Carolina At Greensboro, 312 Eberhart Building, 321 McIver Street, Greensboro, NC, 27402-6170, USA.
Humaira A. Bibi, Department of Biology, The University of North Carolina At Greensboro, 312 Eberhart Building, 321 McIver Street, Greensboro, NC, 27402-6170, USA.
Gabriella Gaje, Department of Biology, The University of North Carolina At Greensboro, 312 Eberhart Building, 321 McIver Street, Greensboro, NC, 27402-6170, USA.
Xiaolun Sun, Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, 72701, USA.
Hong Zhu, Campbell University School of Osteopathic Medicine, Buies Creek, NC, USA.
Y R. Li, Campbell University School of Osteopathic Medicine, Buies Creek, NC, USA.
Zhenquan Jia, Department of Biology, The University of North Carolina At Greensboro, 312 Eberhart Building, 321 McIver Street, Greensboro, NC, 27402-6170, USA. z_jia@uncg.edu.

Document Type

Article

Date of Publication

11-1-2020

Publication Title

Molecular and cellular biochemistry

First Page

27

Last Page

39

Abstract

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.

DOI

10.1007/s11010-020-03831-6

Recommended Citation

Shukla, Halley; Lee, Ho Young; Koucheki, Ashkon; Bibi, Humaira A.; Gaje, Gabriella; Sun, Xiaolun; Zhu, Hong; Li, Y R.; and Jia, Zhenquan, "Targeting glutathione with the triterpenoid CDDO-Im protects against benzo-a-pyrene-1,6-quinone-induced cytotoxicity in endothelial cells" (2020). Osteopathic Medicine, Jerry M. Wallace School of. 2392.
https://cufind.campbell.edu/medicine_school/2392