In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 298, No. 2 ( 2010-02), p. C342-C354
Kurzfassung:
Oxidative stress is one of the causative factors in progression and etiology of age-related cataract. Peroxiredoxin 6 (Prdx6), a savior for cells from internal or external environmental stresses, plays a role in cellular signaling by detoxifying reactive oxygen species (ROS) and thereby controlling gene regulation. Using targeted inactivation of the Prdx6 gene, we show that Prdx6-deficient lens epithelial cells (LECs) are more vulnerable to UV-triggered cell death, a major cause of skin disorders including cataractogenesis, and these cells display abnormal protein profiles. PRDX6-depleted LECs showed phenotypic changes and formed lentoid body, a characteristic of terminal cell differentiation and epithelial-mesenchymal transition. Prdx6 −/− LECs exposed to UV-B showed higher ROS expression and were prone to apoptosis compared with wild-type LECs, underscoring a protective role for Prdx6. Comparative proteomic analysis using fluorescence-based difference gel electrophoresis along with mass spectrometry and database searching revealed a total of 13 proteins that were differentially expressed in Prdx6 −/− cells. Six proteins were upregulated, whereas expression of seven proteins was decreased compared with Prdx6 +/+ LECs. Among the cytoskeleton-associated proteins that were highly expressed in Prdx6-deficient LECs was tropomyosin (Tm)2β. Protein blot and real-time PCR validated dramatic increase of Tm2β and Tm1α expression in these cells. Importantly, Prdx6 +/+ LECs showed a similar pattern of Tm2β protein expression after transforming growth factor (TGF)-β or H 2 O 2 treatment. An extrinsic supply of PRDX6 could restore Tm2β expression, demonstrating that PRDX6 may attenuate adverse signaling in cells and thereby maintain cellular homeostasis. Exploring redox-proteomics ( Prdx6 −/− ) and characterization and identification of abnormally expressed proteins and their attenuation by PRDX6 delivery should provide a basis for development of novel therapeutic interventions to postpone ROS-mediated abnormal signaling deleterious to cells or tissues.
Materialart:
Online-Ressource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00336.2009
Sprache:
Englisch
Verlag:
American Physiological Society
Publikationsdatum:
2010
ZDB Id:
1477334-X
SSG:
12
