Polystyrenenanoplastics lead to ferroptosis in the lungs.
J Adv Res
; 56: 31-41, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-36933884
ABSTRACT
INTRODUCTION:
It has been shown that polystyrenenanoplastic (PS-NP) exposure induces toxicity in the lungs.OBJECTIVES:
This study aims to provide foundational evidence to corroborate that ferroptosis and abnormal HIF-1α activity are the main factors contributing to pulmonary dysfunction induced by PS-NP exposure.METHODS:
Fifty male and female C57BL/6 mice were exposed to distilled water or 100â¯nm or 200â¯nm PS-NPs via intratracheal instillation for 7 consecutive days. Hematoxylin and eosin (H&E) and Masson trichrome staining were performed to observe the histomorphological changes in the lungs. To clarify the mechanisms of PS-NP-induced lung injury, we used 100⯵g/ml, 200⯵g/ml and 400⯵g/ml 100 or 200â¯nm PS-NPs to treat the human lung bronchial epithelial cell line BEAS-2B for 24â¯h. RNA sequencing (RNA-seq) of BEAS-2B cells was performed following exposure. The levels of glutathione, malondialdehyde, ferrous iron (Fe2+), and reactive oxygen species (ROS) were measured. The expression levels of ferroptotic proteins were detected in BEAS-2B cells and lung tissues by Western blotting. Western blotting, immunohistochemistry, and immunofluorescence were used to evaluate the HIF-1α/HO-1 signaling pathway activity.RESULTS:
H&E staining revealed substantial perivascular lymphocytic inflammation in a bronchiolocentric pattern, and Masson trichrome staining demonstrated critical collagen deposits in the lungs after PS-NP exposure. RNA-seq revealed that the differentially expressed genes in PS-NP-exposed BEAS-2B cells were enriched in lipid metabolism and iron ion binding processes. After PS-NP exposure, the levels of malondialdehyde, Fe2+, and ROS were increased, but glutathione level was decreased. The expression levels of ferroptotic proteins were altered significantly. These results verified that PS-NP exposure led to pulmonary injury through ferroptosis. Finally, we discovered that the HIF-1α/HO-1 signaling pathway played an important role in regulating ferroptosis in the PS-NP-exposed lung injury.CONCLUSION:
PS-NP exposure caused ferroptosis in bronchial epithelial cells by activating the HIF-1α/HO-1 signaling pathway, and eventually led to lung injury.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Lesão Pulmonar
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Ferroptose
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article