GSE161701
Autophagy facilitates age-related cell apoptosis - a new insight from senile cataract
Age-related cell loss underpins many senescence-associated diseases. Senile cataract is a primary blindness-causing age-related ocular disease. Apoptosis of lens epithelial cells (LECs) is the common cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, the mechanism of which remains elusive. Here we reported the concomitance of increased autophagy and apoptosis in the same LEC from senile cataract patients. Oxidative stress triggered autophagy preceded apoptosis, while blocking autophagy by ablation of Atg7 or Atg3 gene remarkably suppressed apoptosis in HLE-B3 cell line. We identified autophagy adaptor SQSTM1/p62 as the critical scaffold protein to sustain a pro-survival signaling PKC?-NF-?B cascades, which antagonized the pro-apoptotic signaling in LECs. Importantly, prolonged autophagy in human senescent LECs responding to oxidative stress induced extensive degradation of p62 protein and therefore facilitated apoptosis. Moreover, pharmacological inhibitor of autophagy, 3-MA, significantly rescued apoptosis of human senescent LECs challenged by oxidative stress. Collectively, our data demonstrated that hyperactivation of autophagy aggravates age-related apoptotic cell death via inhibiting the p62-PKC?-NF-?B pro-survival axis in human senescent LECs. This work expands the understanding of the etiology of senile cataract and provides insight for mechanisms of age-related cell death in senescence-associated diseases. Overall design: wild type(WT) HLE-B3 or Atg7KO HLE-B3 cells treated with or without 200 µM H2O2 for 12 hrs(three biological replicates per group)