Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2
Exposure to environmental pollutants, including dioxin-like polychlorinated biphenyls (PCBs), play an important role in vascular inflammation and cardiometabolic diseases (CMDs) by inducing oxidative stress. Earlier, we demonstrated that oxidative stress-mediated lipid peroxidation derived 4-hydroxy...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/10/6/328 |
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| author | Bipradas Roy Zhao Yang Guodong Pan Katherine Roth Manisha Agarwal Rahul Sharma Michael C. Petriello Suresh Selvaraj Palaniyandi |
| author_facet | Bipradas Roy Zhao Yang Guodong Pan Katherine Roth Manisha Agarwal Rahul Sharma Michael C. Petriello Suresh Selvaraj Palaniyandi |
| author_sort | Bipradas Roy |
| collection | DOAJ |
| description | Exposure to environmental pollutants, including dioxin-like polychlorinated biphenyls (PCBs), play an important role in vascular inflammation and cardiometabolic diseases (CMDs) by inducing oxidative stress. Earlier, we demonstrated that oxidative stress-mediated lipid peroxidation derived 4-hydroxy-2-nonenal (4HNE) contributes to CMDs by decreasing the angiogenesis of coronary endothelial cells (CECs). By detoxifying 4HNE, aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, enhances CEC angiogenesis. Therefore, we hypothesize that ALDH2 activation attenuates a PCB 126-mediated 4HNE-induced decrease in CEC angiogenesis. To test our hypothesis, we treated cultured mouse CECs with 4.4 µM PCB 126 and performed spheroid and aortic ring sprouting assays, the ALDH2 activity assay, and Western blotting for the 4HNE adduct levels and real-time qPCR to determine the expression levels of <i>Cyp1b1</i> and oxidative stress-related genes. PCB 126 increased the gene expression and 4HNE adduct levels, whereas it decreased the ALDH2 activity and angiogenesis significantly in MCECs. However, pretreatment with 2.5 µM disulfiram (DSF), an ALDH2 inhibitor, or 10 µM Alda 1, an ALDH2 activator, before the PCB 126 challenge exacerbated and rescued the PCB 126-mediated decrease in coronary angiogenesis by modulating the 4HNE adduct levels respectively. Finally, we conclude that ALDH2 can be a therapeutic target to alleviate environmental pollutant-induced CMDs. |
| first_indexed | 2024-03-09T22:20:36Z |
| format | Article |
| id | doaj.art-db869558e8bb49788bb2e3c8ffeb43cc |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-09T22:20:36Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-db869558e8bb49788bb2e3c8ffeb43cc2023-11-23T19:16:25ZengMDPI AGToxics2305-63042022-06-0110632810.3390/toxics10060328Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2Bipradas Roy0Zhao Yang1Guodong Pan2Katherine Roth3Manisha Agarwal4Rahul Sharma5Michael C. Petriello6Suresh Selvaraj Palaniyandi7Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USAInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USADivision of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USAInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USADepartment of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48202, USAInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USAInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USADivision of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USAExposure to environmental pollutants, including dioxin-like polychlorinated biphenyls (PCBs), play an important role in vascular inflammation and cardiometabolic diseases (CMDs) by inducing oxidative stress. Earlier, we demonstrated that oxidative stress-mediated lipid peroxidation derived 4-hydroxy-2-nonenal (4HNE) contributes to CMDs by decreasing the angiogenesis of coronary endothelial cells (CECs). By detoxifying 4HNE, aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, enhances CEC angiogenesis. Therefore, we hypothesize that ALDH2 activation attenuates a PCB 126-mediated 4HNE-induced decrease in CEC angiogenesis. To test our hypothesis, we treated cultured mouse CECs with 4.4 µM PCB 126 and performed spheroid and aortic ring sprouting assays, the ALDH2 activity assay, and Western blotting for the 4HNE adduct levels and real-time qPCR to determine the expression levels of <i>Cyp1b1</i> and oxidative stress-related genes. PCB 126 increased the gene expression and 4HNE adduct levels, whereas it decreased the ALDH2 activity and angiogenesis significantly in MCECs. However, pretreatment with 2.5 µM disulfiram (DSF), an ALDH2 inhibitor, or 10 µM Alda 1, an ALDH2 activator, before the PCB 126 challenge exacerbated and rescued the PCB 126-mediated decrease in coronary angiogenesis by modulating the 4HNE adduct levels respectively. Finally, we conclude that ALDH2 can be a therapeutic target to alleviate environmental pollutant-induced CMDs.https://www.mdpi.com/2305-6304/10/6/328angiogenesis3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB 126)environmental pollutantscoronary endothelial cellsaldehyde dehydrogenase 24-hydroxy-2-nonenal |
| spellingShingle | Bipradas Roy Zhao Yang Guodong Pan Katherine Roth Manisha Agarwal Rahul Sharma Michael C. Petriello Suresh Selvaraj Palaniyandi Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2 Toxics angiogenesis 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB 126) environmental pollutants coronary endothelial cells aldehyde dehydrogenase 2 4-hydroxy-2-nonenal |
| title | Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2 |
| title_full | Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2 |
| title_fullStr | Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2 |
| title_full_unstemmed | Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2 |
| title_short | Exposure to the Dioxin-like Pollutant PCB 126 Afflicts Coronary Endothelial Cells via Increasing 4-Hydroxy-2 Nonenal: A Role for Aldehyde Dehydrogenase 2 |
| title_sort | exposure to the dioxin like pollutant pcb 126 afflicts coronary endothelial cells via increasing 4 hydroxy 2 nonenal a role for aldehyde dehydrogenase 2 |
| topic | angiogenesis 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB 126) environmental pollutants coronary endothelial cells aldehyde dehydrogenase 2 4-hydroxy-2-nonenal |
| url | https://www.mdpi.com/2305-6304/10/6/328 |
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