Cytotoxic Effects of Transthyretin Aggregates in an Epidermoid Cell Line.

OBJECTIVE: Skin amyloid deposits can occur as part of systemic amyloidoses including those involving misfolded- aggregated transthyretins (agTTR). Pathological effects of agTTR on the skin are not well understood. The main objective of the current study was to examine the toxicity of agTTR upon a human keratinocyte cell line.

METHODS: Cells were analyzed for indicators of oxidative stress after treatment with normal soluble TTR or the same pre-aggregation concentration of agTTR. Hydrogen peroxide production was analyzed as an indicator for the involvement of reactive oxygen species.

RESULTS: Treatment of cells with agTTR significantly increased hydrogen peroxide production (p < 0.05 vs. controls). Glutathione (GSH) and catalase were analyzed as indicators of endogenous cellular antioxidant activity. Treatment of cells with agTTR resulted in significant decreases in both catalase activity and GSH levels (p < 0.05 vs. controls).

CONCLUSION: agTTR disrupts redox balance and induces oxidative stress in these epidermoid cells.