Silica Nanoparticles Induce SH-SY5Y Cells Death Via PARP and Caspase Signaling Pathways

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Silica nanoparticles (SiNPs) are increasingly linked to neurodegenerative diseases.
• The precise mechanisms of SiNP-induced neuroblast injury are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms underlying SiNP-induced neuroblast (SH-SY5Y cells) death.
• To elucidate the roles of oxidative stress, mitochondrial dysfunction, Parthanatos, and caspase-dependent apoptosis in SiNP toxicity.

Main Methods:

• In vitro exposure of SH-SY5Y cells to SiNPs.
• Assays for cell viability (MTT), ROS and Ca2+ levels (flow cytometry), apoptosis (Hoechst/TUNEL staining).
• Biochemical analysis of SOD, ATPase, ATP; gene expression (qPCR); protein analysis (Western Blot, immunofluorescence); inhibitor studies (Olaparib, Z-VAD).

Main Results:

• SiNPs reduced cell viability, increased ROS and Ca2+ overload, and decreased SOD and ATPase activity.
• SiNPs altered mitochondrial function, upregulated PARP pathway genes, and increased PARP/Caspase pathway proteins.
• Inhibitors of PARP and Caspase pathways significantly ameliorated SiNP-induced cell death.

Conclusions:

• SiNPs induce SH-SY5Y cell death through excessive ROS production and mitochondrial dysfunction.
• Cell death occurs via interconnected Parthanatos and caspase-dependent apoptotic pathways.
• Targeting PARP and Caspase pathways may offer therapeutic strategies against SiNP neurotoxicity.