Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling
© 2024. The Author(s)..
BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described.
RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation.
CONCLUSIONS: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Particle and fibre toxicology - 21(2024), 1 vom: 01. Apr., Seite 17 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Xueyan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
7631-86-9 |
|---|
| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 04.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12989-024-00579-5 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370513460 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370513460 | ||
| 003 | DE-627 | ||
| 005 | 20240404235326.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240403s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12989-024-00579-5 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1364.xml |
| 035 | |a (DE-627)NLM370513460 | ||
| 035 | |a (NLM)38561847 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Xueyan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.04.2024 | ||
| 500 | |a Date Revised 04.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described | ||
| 520 | |a RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation | ||
| 520 | |a CONCLUSIONS: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a HO-1 | |
| 650 | 4 | |a Myocardial injury | |
| 650 | 4 | |a Silica nanoparticles | |
| 650 | 4 | |a miR-125b | |
| 650 | 7 | |a Silicon Dioxide |2 NLM | |
| 650 | 7 | |a 7631-86-9 |2 NLM | |
| 650 | 7 | |a Iron |2 NLM | |
| 650 | 7 | |a E1UOL152H7 |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 700 | 1 | |a Xu, Hailin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xinying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Songqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Zhiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yanbo |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Caixia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Particle and fibre toxicology |d 2004 |g 21(2024), 1 vom: 01. Apr., Seite 17 |w (DE-627)NLM154647845 |x 1743-8977 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2024 |g number:1 |g day:01 |g month:04 |g pages:17 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12989-024-00579-5 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2024 |e 1 |b 01 |c 04 |h 17 | ||