Nrf-2-driven long noncoding RNA ODRUL contributes to modulating silver nanoparticle-induced effects on erythroid...

Area of Science:

• Nanotechnology
• Molecular Biology
• Toxicology

Background:

• Silver nanoparticles (AgNPs) raise biosafety concerns due to their biological effects on human health.
• Current research on AgNP toxicity primarily focuses on oxidative stress pathways, but the underlying molecular mechanisms remain unclear.
• Understanding AgNP effects on erythroid cells requires deeper insight into molecular signaling.

Purpose of the Study:

• To elucidate the molecular basis of AgNP-induced effects on erythroid cells using long noncoding RNAs (lncRNAs).
• To identify specific lncRNAs involved in AgNP toxicity and their regulatory pathways.

Main Methods:

• Investigated AgNP effects on K562 erythroid cells.
• Identified and characterized the lncRNA ODRUL.
• Examined the role of oxidative stress and Nrf2 in ODRUL expression.
• Analyzed the interaction of ODRUL with PI4Kα and its downstream effects on AKT/JNK and Bcl-2 signaling.

Main Results:

• ODRUL expression was significantly upregulated in erythroid cells exposed to AgNPs, correlating with increased cell death.
• Oxidative stress-activated Nrf2 transcriptionally promoted ODRUL expression.
• ODRUL interacted with PI4Kα, modulating AKT and JNK signaling pathways.
• AgNP-induced stress led to negative regulation of Bcl-2 via PI4K-AKT/JNK signaling, resulting in enhanced cell death.

Conclusions:

• Nrf2-mediated lncRNA ODRUL is crucial for AgNP-induced toxicity in erythroid cells.
• ODRUL regulates AKT/JNK-Bcl-2 signaling through physical interaction with PI4Kα.
• This study provides novel molecular insights into AgNP toxicity mechanisms in erythroid cells.