Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells

作者：Zhang, Jun; Xiang, Xiaohong; Shu, Shuangshuang; Zhang, Cuiling; Liang, Yuling; Jiang, Tingting; Zhang, Wenying; Guo, Tingting; Liang, Xiujie^*; Tang, Xun^*

来源：Experimental and Therapeutic Medicine, 2018, 15(4): 3908-3916.

DOI：10.3892/etm.2018.5875

• advanced oxidation protein products
• autophagy
• chronic kidney disease
• phosphoinositide 3-kinase
• protein kinase B
• mammalian target of rapamycin signaling pathway
• renal tubular epithelial cell injury

It is well known that autophagy serves a crucial role in renal tubular epithelial cell (RTEC) injury in the pathogenesis of chronic kidney disease (CKD). The accumulation of advanced oxidation protein products (AOPPs) also participates in the progression of CKD. However, the effects of AOPPs on autophagy remain unknown. To clarify the underlying mechanism of RTEC injury in CKD, the effect of AOPPs on HK-2 cells, an RTEC cell line, was investigated. The results of the present study revealed that AOPP exposure downregulated the expression of B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1, reduced the conversion of microtubule-associated proteins 1 light chain 3B (LC3)-I to LC3-II and the formation of autophagosomes, and lead to an accumulation of p62. These results suggest that AOPPs may inhibit the autophagic activity of HK-2 cells. Furthermore, the aforementioned changes were mediated by the AOPP-phosphorylated phosphoinositide 3-kinase3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway; this was verified by treatment with LY294002, a PI3K inhibitor, which reversed the AOPP-induced changes. The present study also demonstrated that the activation of autophagy with rapamycin led to an improvement in the AOPP-induced overexpression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, two biomarkers of RTEC injury, whereas inhibiting autophagy with chloroquine further increased their expression during AOPP treatment. Collectively, these results indicate that AOPPs may inhibit autophagy in RTECs via activation of the PI3K/AKT/mTOR pathway and that autophagy inhibition serves a role in AOPP-induced RTEC injury.

• 出版日期2018-4
• 单位南方医科大学