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

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.
AuthorsChun-Hung Su, Yung-Chuan Ho, Min-Wei Lee, Ching-Chi Tseng, Shiuan-Shinn Lee, Ming Kun Hsieh, Hsin-Hung Chen, Chien-Ying Lee, Sheng-Wen Wu, Yu-Hsiang Kuan
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 9314342 ( 2021) ISSN: 1942-0994 [Electronic] United States
PMID34336119 (Publication Type: Journal Article)
CopyrightCopyright © 2021 Chun-Hung Su et al.
Chemical References
  • Apoptosis Inducing Factor
  • Pyrenes
  • Reactive Oxygen Species
  • AMP-Activated Protein Kinases
  • 1-nitropyrene
Topics
  • AMP-Activated Protein Kinases (metabolism)
  • Apoptosis (physiology)
  • Apoptosis Inducing Factor (metabolism)
  • Humans
  • Macrophages (metabolism)
  • Pyrenes (adverse effects)
  • Reactive Oxygen Species (metabolism)

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