HSP90 acts as a senomorphic target in senescent retinal pigmental epithelial cells
Dandan Chen, Xuyan Peng, Yuxuan Wang, Mingjun Jiang, Mengjiao Xue, Guohui Shang, Xuhui Liu, Xiaolin Jia, Baixue Liu, Yingwei Lu, Hongmei Mu, Fengyan Zhang, Yanzhong Hu
Abstract
. In addition, we found that inhibition of HSP90 by IPI504 reduces SA-β-Gal's protein expression and enzyme activity in a dose-dependent manner. HSP90 interacts with and regulates SA-β-Gal protein stabilization in senescent ARPE-19 cells. Taken together, these results suggest that HSP90 regulates the SASP and SA-β-Gal activity in senescent RPE cells through associating with distinctive mechanism including NF-κB, HIF1α and lysosomal SA-β-Gal. HSP90 inhibitors (e.g. IPI504) could be a promising senomorphic drug candidate for AMD intervention.
Topics & Concepts
Hsp90Cell biologySenescenceRetinal pigment epitheliumBiologyRetinalAutophagyMacular degenerationHsp90 inhibitorMolecular biologyBiochemistryApoptosisHeat shock proteinMedicineGeneOphthalmologyHeat shock proteins researchConnexins and lens biologyAntioxidant Activity and Oxidative Stress