Abstract
Purpose :
The purpose of the current study is to identify the new role of the glutaredoxin (Grx) system in regulating cellular senescence, utilizing glutaredoxin 1 (Grx1) and glutaredoxin 2 (Grx2) double knockout (DKO) mice as the investigative model.
Methods :
Primary lens epithelial cells (LECs) were extracted from both wild-type (WT) and DKO mice and analyzed for various senescence markers, including p53, p16, p21, proliferating cell nuclear antigen (PCNA), phosphorylated RB (Phospho-RB), senescence-associated secretory phenotype (SASP), and Lamin B.
Results :
Our examination of primary LECs from DKO mice revealed a significant increase in p53 levels and enhanced Phospho-RB, highlighting an augmented senescent response and disruption of the cell cycle due to Grx1/Grx2 deficiency (n=3; P<0.05). Notably, Lamin B levels were found to be lower in DKO cells, indicating a potential link to altered nuclear architecture in senescent LECs (n=3; P<0.05). Additionally, PCNA levels were decreased in DKO cells, consistent with the reduced proliferative capacity of senescent cells (n=3; P<0.05). In contrast, senescence markers such as p16, p21, and SASP factors were not expressed in either DKO or WT cells, suggesting a specific impact of the Grx system on senescence-related pathways in the lens. This pattern of marker expression unveils the intricate role of the Grx system in the cellular aging process.
Conclusions :
The study provides novel insights into the complex role of the Grx system in cellular aging. The observed alteration in key senescence markers like p53, Phospho-RB, and Lamin B in DKO LECs underscores the potential influence of the Grx system on the senescence process. However, the lack of change in other pathways including p16, p21, and SASP suggests a selective role of the Grx system in the lens. These findings open new avenues for targeted therapeutic strategies to modulate the Grx system and combat senescence-related diseases, particularly in the lens.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.