Regulating anaerobic metabolism and promoting myocardial ischemia-hypoxia injury by diesel particulate matter and its key component benzo[a]pyrene via targeting oxygen sensors
| Title: | Regulating anaerobic metabolism and promoting myocardial ischemia-hypoxia injury by diesel particulate matter and its key component benzo[a]pyrene via targeting oxygen sensors |
|---|---|
| Authors: | Hao YIN, Ze ZHANG, Liu WU, Yingzhu WANG, Yuxin ZHENG, Xiaoting JIN |
| Source: | 环境与职业医学, Vol 40, Iss 5, Pp 491-499 (2023) |
| Publisher Information: | Editorial Committee of Journal of Environmental and Occupational Medicine, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine (General) LCC:Toxicology. Poisons |
| Subject Terms: | diesel particulate matter, benzo[a]pyrene, ischemia-hypoxia injury, hypoxia-inducible factor-1 alpha, oxygen sensor, anaerobic metabolism, Medicine (General), R5-920, Toxicology. Poisons, RA1190-1270 |
| More Details: | BackgroundThe exposure to diesel particulate matter (DPM) and its polycyclic aromatic hydrocarbons (PAH) is closely related to the morbidity and mortality of ischemic heart disease (IHD). However, it is unclear what key components and targets of DPM exposure involve in myocardial ischemia-hypoxia injury and associated mechanisms.ObjectiveTo identify key PAH components of DPM that act on myocardial hypoxic injury, andclarify the role of oxygen sensors-regulated anaerobic metabolism in DPM and key components-induced hypoxic injury and the targets of the key PAH components.MethodsHuman cardiomyocyte cell line AC16 cells were exposed to 0, 1, 5, and 10 μg·mL−1 DPM in a high glucose DMEM medium with 10% fetal bovine serum (FBS) (HGM) or low FBS (0.5%) in high glucose DMEM medium (LFM), for 12 h under 2% O2, and expression of hypoxia-inducible factor-1α (HIF-1α), Bax, and Cleaved-caspase3 was determined by Western blotting. Under normal condition, the cell viability was detected after PAH exposure for 12 h. Under the condition of ischemia-hypoxia model, cells were exposed to 0, 0.005, 0.5, and 5 µg·mL−1 PAH for 12 h, and the protein expression of HIF-1α, Bax, and Cleaved-caspase3 was determined. After exposure to DPM or PAH for 12 h, the contents of pyruvate and lactate in cells were detected. Pretreatment with glycolysis inhibitor GSK2837808A was used to explore the role of glycolysis in DPM and benzo[a]pyrene (BaP)-induced hypoxia injury. A molecular docking technique was used to analyze the binding affinity between PAH and oxygen sensors (prolyl hydroxylase domain-containing protein 2, PHD2, and factor-inhibiting hypoxia-inducible factor 1, FIH1), and the protein levels of PHD2, FIH1, and hydroxyl-HIF-1-alpha (OH-HIF-1α) after the DPM or BaP treatment were further determined.ResultsUnder hypoxia, DPM exposure in the LFM induced the expression of HIF-1α, Bax, and Cleaved-caspase3 (P0.05), other PAH decreased cell viability when the concentration was above 1 μg·mL−1 (P |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English Chinese |
| ISSN: | 2095-9982 |
| Relation: | http://www.jeom.org/article/cn/10.11836/JEOM22416; https://doaj.org/toc/2095-9982 |
| DOI: | 10.11836/JEOM22416 |
| Access URL: | https://doaj.org/article/79d8eb0f4cb147bd97f49b3f4145affb |
| Accession Number: | edsdoj.79d8eb0f4cb147bd97f49b3f4145affb |
| Database: | Directory of Open Access Journals |
| ISSN: | 20959982 |
|---|---|
| DOI: | 10.11836/JEOM22416 |
| Published in: | 环境与职业医学 |
| Language: | English Chinese |