期刊
BIOCHEMICAL PHARMACOLOGY
卷 162, 期 -, 页码 132-141出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2018.10.016
关键词
Cadmium; Puerarin; Autophagy; Oxidative stress; Proximal tubular cells
资金
- National Natural Science Foundation of China [31472251, 31873030]
- Funds of Shandong Double Tops Program
Previous studies have shown that oxidative stress-induced inhibition of autophagy plays a pivotal role in cadmium (Cd)-mediated cytotoxicity in primary rat proximal tubular (rPT) cells. The objective of this study is to explore the protective effect of puerarin (PU), a potent antioxidant, on Cd-induced autophagy inhibition and oxidative stress in rPT cells. First, Cd-induced blockage of autophagic flux in rPT cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. Also, Cd-induced lysosomal alkalinization and impairment of lysosomal degradation capacity were obviously recovered by PU, demonstrating that PU can restore Cd-induced lysosomal dysfunction. Moreover, Cd-induced lysosomal membrane permeabilization (LMP) was effectively blocked by PU. Cd-stimulated Nrf2 nuclear translocation and subsequent elevated expression of Nrf2-downstream targets were significantly inhibited by PU treatment. Simultaneously, Cd-elevated protein levels of antioxidant enzymes and glutathione synthesis related proteins in rPT cells were markedly downregulated by PU treatment. In conclusion, these observations indicate that PU alleviates Cd-induced cytotoxicity in rPT cells through restoring autophagy, blocking LMP and inhibiting Nrf2 pathway, which is intimately related with its antioxidant activity.
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