Cuproptosis Aggravates Pulpitis by Inhibiting the Pentose Phosphate Pathway

Area of Science:

• Biochemistry
• Cell Biology
• Oral Biology

Background:

• Excessive copper is toxic and can induce programmed cell death (cuproptosis).
• The role of copper metabolism and cuproptosis in pulpitis is not well understood.
• Pulpitis involves inflammation triggered by bacterial components.

Purpose of the Study:

• To investigate the mechanism of copper deposition and cuproptosis in pulpitis.
• To determine the role of the pentose phosphate pathway (PPP) in copper detoxification during pulpitis.
• To explore potential therapeutic strategies targeting copper metabolism in pulpitis.

Main Methods:

• Inductively coupled plasma mass spectrometry to quantify copper levels in pulpitis tissues.
• ¹³C-glucose stable isotope tracing to assess glucose metabolism and PPP activity.
• In vivo and in vitro experiments stimulating cells with lipoteichoic acid (LTA) or lipopolysaccharides (LPS).

Main Results:

• Pulpitis tissues showed significantly higher copper concentrations than healthy tissues.
• LTA or LPS stimulation led to increased copper deposition and cuproptosis.
• Copper accumulation impeded the PPP, reducing NADPH generation and impairing cellular defense against copper toxicity.
• The PPP was found to regulate the phenotype, function, and survival of preodontoblast-like cells.

Conclusions:

• Bacterial components trigger copper deposition and cuproptosis in pulpitis by inhibiting the PPP.
• Disruption of copper homeostasis and metabolic reprogramming are key features of pulpitis.
• Targeting copper metabolism and the PPP presents a potential host-targeted therapeutic strategy for pulpitis.