PM2.5;
4-PBA;
intracellular Ca2+;
ER stress;
mitochondrial damage;
pyroptosis;
ER STRESS;
PM2.5;
EXPOSURE;
INFLAMMATION;
D O I:
10.3390/biom14091135
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Fine particulate matter (PM2.5) is a significant cause of respiratory diseases and associated cellular damage. The mechanisms behind this damage have not been fully explained. This study investigated two types of cellular damage (inflammation and pyroptosis) induced by PM2.5, focusing on their relationship with two organelles (the endoplasmic reticulum and mitochondria). Animal models have demonstrated that PM2.5 induces excessive endoplasmic reticulum stress (ER stress), which is a significant cause of lung damage in rats. This was confirmed by pretreatment with an ER stress inhibitor (4-Phenylbutyric acid, 4-PBA). We found that, in vitro, the intracellular Ca2+ ([Ca2+]i) dysregulation induced by PM2.5 in rat alveolar macrophages was associated with ER stress. Changes in mitochondria-associated membranes (MAMs) result in abnormal mitochondrial function. This further induced the massive expression of NLRP3 and GSDMD-N, which was detrimental to cell survival. In conclusion, our findings provide valuable insights into the relationship between [Ca2+]i dysregulation, mitochondrial damage, inflammation and pyroptosis under PM2.5-induced ER stress conditions. Their interactions ultimately have an impact on respiratory health.
机构:
Tianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R ChinaTianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R China
Liu Xin
Wu Fan
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机构:
Tianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R ChinaTianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R China
Wu Fan
Du Tingting
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机构:
Tianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R ChinaTianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R China
Du Tingting
Sun Zuoming
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机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USATianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R China
Sun Zuoming
Zhang Qiang
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机构:
Tianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R ChinaTianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R China
机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Wang, Chunyuan
Meng, Xianzong
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, NetherlandsDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Meng, Xianzong
Meng, Meiling
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Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Meng, Meiling
Shi, Min
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Shi, Min
Sun, Wenping
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Sun, Wenping
Li, Xiaojing
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Li, Xiaojing
Zhang, Xiao
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Zhang, Xiao
Liu, Ruihao
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Liu, Ruihao
Fu, Ying
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China
Fu, Ying
Song, Laiyu
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机构:
Dalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R ChinaDalian Med Univ, Coll Med Lab, Dalian 116044, Liaoning, Peoples R China