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  • Quercetin alleviates Cadmium-induced autophagy inhibition via TFEB-dependent lysosomal restoration in primary proximal tubular cells.

Quercetin alleviates Cadmium-induced autophagy inhibition via TFEB-dependent lysosomal restoration in primary proximal tubular cells.

Ecotoxicology and environmental safety (2021-01-06)
Yuan Zhao, Zi-Fa Li, Dong Zhang, Zhen-Yong Wang, Lin Wang
ABSTRACT

Autophagy dysregulation plays a pivotal role in cadmium (Cd)-induced nephrotoxicity. Quercetin (Qu), a flavonoid antioxidant with autophagy-enhancing effect, has protective effect on Cd-induced toxicity, but whether it can prevent Cd-induced nephrotoxicity via restoration of autophagy remains unknown. Here, primary rat proximal tubular (rPT) cells were exposed to Cd and/or Qu in vitro to clarify this issue. Data first showed that Cd-impaired autophagic flux was markedly alleviated by Qu, including decreased levels of autophagy marker proteins and recovery of autophagosome-lysosome fusion targeted for lysosomes. Meanwhile, Cd-induced lysosomal alkalization due to v-ATPases inhibition was prominently recovered by Qu. Accordingly, Qu enhanced Cd-diminished lysosomal degradation capacity and lysosome-related gene transcription levels. Notably, Qu improved Cd-inhibited TFEB nuclear translocation and its gene transcription level. Furthermore, data showed that the restoration of Cd-impaired autophagy-lysosome pathway and resultant alleviation of cytotoxicity by Qu are TFEB-dependent using TFEB gene silencing and overexpression technologies. In summary, these data provide novel evidences that the protective action of Qu against Cd-induced autophagy inhibition is attributed to its restoration of lysosomal dysfunction, which is dependent on TFEB.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Quercetin, ≥95% (HPLC), solid
Sigma-Aldrich
Cadmium acetate hydrate, ≥99.99% trace metals basis
Sigma-Aldrich
Acridine Orange hydrochloride solution, ≥95.0% (HPLC), 10 mg/mL in H2O
Sigma-Aldrich
Acridine Orange hemi(zinc chloride) salt, For nucleic acid staining in cells or gels
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Sigma-Aldrich
Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
MISSION® esiRNA, targeting human TFEB