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Cytotoxic Effects of Transthyretin Aggregates in an Epidermoid Cell Line
Vai Hong Fong1, Amandio Vieira
1Department of Neurology, Eastern Memorial Hospital, New Taipei, Taiwan, ROC.
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.
Insights
Aggregated transthyretin (agTTR) causes oxidative stress in skin cells. This study shows agTTR disrupts cellular redox balance, increasing hydrogen peroxide and decreasing antioxidant defenses in keratinocytes.
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- Skin amyloid deposits are linked to systemic amyloidoses.
- The specific pathological effects of aggregated transthyretin (agTTR) on skin remain unclear.
Purpose of the Study:
- To investigate the toxicity of agTTR on human keratinocyte cell lines.
- To understand the impact of agTTR on cellular oxidative stress markers.
Main Methods:
- Human keratinocytes were treated with normal soluble TTR or aggregated TTR (agTTR).
- Indicators of oxidative stress, including hydrogen peroxide production, were measured.
- Endogenous antioxidant activity was assessed by analyzing catalase and glutathione (GSH) levels.
Main Results:
- agTTR treatment significantly elevated hydrogen peroxide production in keratinocytes.
- Catalase activity and GSH levels were significantly reduced following agTTR exposure.
- These findings indicate increased reactive oxygen species and diminished antioxidant capacity.
Conclusions:
- Aggregated transthyretin (agTTR) disrupts the redox balance in human epidermoid cells.
- agTTR induces significant oxidative stress in keratinocytes.
- This cellular damage may contribute to the skin manifestations of transthyretin amyloidosis.
