D-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions

作者：Xu, Yao; Li, Yong; Ma, Limei; Xin, Guang; Wei, Zeliang; Zeng, Zhi; Xing, Zhihua; Li, Shiyi; Niu, Hai^*; Huang, Wen^*

来源：Toxicology Letters, 2018, 289: 99-106.

DOI：10.1016/j.toxlet.2018.02.001

• D-galactose
• Premature senescence
• Autophagy flux
• Oxidative stress
• Mitochondrial dysfunction

Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. D-galactose (D-gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that D-gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, D-gal resulted in premature senescence of LECs, which was confirmed by determining the ss-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed. We also verified that D-gal induced the impairment of autophagy flux by measuring the expression of LC3II and P62. Meanwhile, we found that D-gal induced mitochondrial dysfunctions of LECs through increasing reactive oxygen species (ROS), reducing ATP synthesis and mitochondrial potential (MMP), enhancing the concentration of cytoplasm Ca2+ and permeability transition pore (mPTP) opening. Metformin, as a potential anti-aging agent, suppressed the senescence of LECs by restoring autophagy flux and mitochondria functions. Nevertheless, the antioxidant N-acetylcysteine (NAC) scavenged ROS significantly but was not efficient in preventing LECs from premature senescence. Our data suggests that restoring autophagy activity and improving mitochondrial functions may be a potential strategy for the prevention of LECs senescence-related cataract.

• 出版日期2018-6-1
• 单位四川大学