In vivo analysis of protein quality control in response to aging using transgenic mice

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Abstract

Purpose

It has been suggested that aging affects the cells ability to protect protein integrity, which is essential for cellular homeostasis. On cell aging there is impaired protein homeostasis, which can lead to protein insolubilization that is toxic to cells. The carboxyl terminus of Hsp70-interacting protein (CHIP) is an important ubiquitin ligase for protein quality control, and particularly in selective degradation of aggregation prone proteins. The objective of this study was to characterize the transgenic mice that overexpress CHIP/Ubc5 in lens epithelial cells and investigate the role of these proteins in the process that maintains proteins in solution and therefore participates in a number of age-related diseases, including cataract.

Methods

To overexpress CHIP, the α-crystallin promoter was used to drive the expression of CHIP-Ubc5 in lens epithelial cells of transgenic mice. The CHIP levels of transgenic mice (Tg) were determined with western blotting analysis. Cataract was induced by single subcutaneous injection of sodium selenite and the lens transparency was assessed by slit lamp examination. The soluble and insoluble protein content in all groups was evaluated.

Results

The data show that the transgenic mice only overexpress the transgene in lens epithelial cells.The slit lamp analysis showed that transgenic mice appears developed less cataract compared with wild type, with concomitantly increase in ratio of the soluble and insoluble proteins.

Conclusion

Together the data suggest that overexpression of CHIP/Ubc5 in lens epithelial cells could prevent cataract formation by promoting reduction of protein insolubilization.

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