作者: Michael L. Mulhern , Peter F. Kador , Toshimichi Shinohara , Christian J. Madson , James Randazzo
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摘要: Purpose Many cataractogenic stresses also induce endoplasmic reticulum (ER) stress in lens epithelial cells (LECs), which appears to be one of the universal inducers cell death. In galactosemic rats, activation ER results unfolded protein response (UPR)-dependent death pathway, production reactive oxygen species (ROS), and All are induced precede cataract formation. Cellular osmolytes such as 4-phenylbutyric acid (PBA), trimethylamine N-oxide (TMAO), tauroursodeoxychoric (TUDCA) known suppress induction stress. We investigated whether these small molecules prevent formation galactose-fed rat lenses. Methods Cultured LECs were treated with galactose each cellular osmolyte. Sprague-Dawley rats fed a 50% chow for 15 days or without osmolyte treatment. Similarly, selenite was injected subcutaneously into osmolytes. Calcein AM ethidium homodimer-1 (EthD) used detect live dead cells, respectively. The osmolytes, PBA, TMAO, TUDCA tested their ability LEC Results rescued cultured human stressors. administered either orally by injection rats. These had significantly reduced partially delayed hypermature Since UPR not activated selenite, we nuclear UPR-independent pathway control. selenite-induced did alleviate Conclusions further establish that play vital role certain types addition, may potential prophylactic drugs some cataracts.