1-Nitropyrene Induced Reactive Oxygen Species–Mediated Apoptosis in Macrophages through AIF Nuclear Translocation and AMPK/Nrf-2/HO-1 Pathway Activation

Author:

Su Chun-Hung123,Ho Yung-Chuan4,Lee Min-Wei5,Tseng Ching-Chi6,Lee Shiuan-Shinn7,Hsieh Ming Kun5,Chen Hsin-Hung8910,Lee Chien-Ying1112,Wu Sheng-Wen1314,Kuan Yu-Hsiang1112ORCID

Affiliation:

1. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

2. Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

3. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

4. School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan

5. A Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taichung, Taiwan

6. Aerospace Center Hospital, Peking University, Beijing, China

7. School of Public Health, Chung Shan Medical University, Taichung, Taiwan

8. Division of Endocrinology and Metabolism, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan

9. School of Medicine, Institute of Medicine and Public Health, Chung Shan Medical University, Taichung, Taiwan

10. Chung Sheng Clinic, Nantou, Taiwan

11. Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

12. Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan

13. Division of Nephrology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

14. The School of Medicine, Chung Shan Medical University, Taichung, Taiwan

Abstract

1-Nitropyrene (1-NP), one of the most abundant nitropolycyclic aromatic hydrocarbons (nitro-PAHs), is generated from the incomplete combustion of carbonaceous organic compounds. 1-NP is a specific marker of diesel exhaust and is an environmental pollutant and a probable carcinogen. Macrophages participate in immune defense against the invasive pathogens in heart, lung, and kidney infection diseases. However, no evidence has indicated that 1-NP induces apoptosis in macrophages. In the present study, 1-NP was found to induce concentration-dependent changes in various cellular functions of RAW264.7 macrophages including cell viability reduction; apoptosis generation; mitochondrial dysfunction; apoptosis-inducing factor (AIF) nuclear translocation; intracellular ROS generation; activation of the AMPK/Nrf-2/HO-1 pathway; changes in the expression of BCL-2 family proteins; and depletion of antioxidative enzymes (AOE), such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) These results indicate that 1-NP induced apoptosis in macrophages through AIF nuclear translocation and ROS generation due to mitochondrial dysfunction and to the depletion of AOE from the activation of the AMPK/Nrf-2/HO-1 pathway.

Funder

Chung Shan Medical University Hospital

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

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