Nickel oxide nanoparticles induce apoptosis and ferroptosis in airway epithelial cells via ATF3

Abstract

Exposure to nickel oxide nanoparticles (NiONPs), which have been widely produced and applied in industry, leads to adverse pulmonary and systemic effects. The aim of this study is to investigate the involvement of apoptosis and ferroptosis in NiONPsinduced acute lung injury (ALI). Intratracheal instillation of NiONPs into mice elevated the levels of pro-inflammatory cytokines, neutrophils, and proteins in the bronchoalveolar lavage fluid, and triggered apoptosis and ferroptosis in the lung tissues. Consistently, NiONPs-induced apoptosis and ferroptosis were observed in in vitro experiments using human lung epithelial cells. Activating transcription factor 3 (ATF3), a stress-inducible transcription factor, was upregulated by NiONPs exposure in both murine lung tissues and human lung epithelial cells. Moreover, human lung epithelial cells with ATF3 deficiency exhibited a lower level of apoptosis and ferroptosis when exposed to NiONPs. Collectively, our findings demonstrated that ATF3 was responsive to NiONPs exposure, and promoted NiONPs-induced apoptosis and ferroptosis in lung epithelial cells, indicating that ATF3 is a potential biomarker and therapeutic target for NiONPs-associated ALI.

Decreased thioredoxin reductase 3 expression promotes nickel‐induced damage to cardiac tissue via activating oxidative stress‐induced apoptosis and inflammation

“…21 Exposure to Ni has been associated with carcinogenicity, hematotoxicity, developmental toxicity, reproductive toxicity, pulmonary toxicity, and hepatorenal dysfunction. [22][23][24][25][26] The heart is one of the essential organs of the human body and the driving force in the circulatory system. Overexposure to Ni can also cause cardiovascular disease and heart damage.…”

“…Acute Ni poisoning has lethal effect, and chronic Ni exposure is also harmful to human health 21 . Exposure to Ni has been associated with carcinogenicity, hematotoxicity, developmental toxicity, reproductive toxicity, pulmonary toxicity, and hepatorenal dysfunction 22–26 . The heart is one of the essential organs of the human body and the driving force in the circulatory system.…”

The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways

“…It is noteworthy that ACSL4, which is thought to be a specific and sensitive marker in the regulation of glioblastoma and ferroptosis, significantly varies inversely with GPx4 in glioma 23 . Nickel oxide nanoparticles induced apoptosis and ferroptosis in epithelial cells via ATF3 24 . Cadmium, another trace element, induced ferroptosis and apoptosis by modulating miR‐34a‐5p/Sirt1axis in PC12 cells 25 .…”

“…23 Nickel oxide nanoparticles induced apoptosis and ferroptosis in epithelial cells via ATF3. 24 Cadmium, another trace element, induced ferroptosis and apoptosis by modulating miR-34a-5p/ Sirt1axis in PC12 cells. 25 To our knowledge, there are no approved ferroptosis-inducing molecules on glioblastoma, although there are FDA-approved ferroptosis-inducing compounds for different possible targets.…”

Nickel oxide nanoparticles induce developmental neurotoxicity in zebrafish by triggering both apoptosis and ferroptosis

“…[19][20][21] Importantly, similar to other nanocrystalline metal oxides, NiO-NPs induced activation of apoptosis and ferroptosis, the two main forms of programmed cell death, have also been suggested to be involved in their toxic effects. 22,23 It's worth noting that various nanoparticles may enter the central nervous system (CNS) and trigger off oxidative stress and neuroinflammation, thereby leading to neurodegenerative diseases. 24 Given the similarities and differences between nanoparticles, a hypothesis about whether NiO-NPs impair CNS development and function has been seriously raised and needs to be immediately addressed.…”