Cadmium exposure induces autophagy via PLC‐IP3‐IP3R signaling pathway in duck renal tubular epithelial cells. Issue 11 (4th August 2022)

• Record Type: Journal Article
• Authors: Guo, Huiling; Huang, Bingyan; Cui, Ting; Chu, Xuesheng; Pu, Wenjing; Huang, Gang; Xing, Chenghong; Zhang, Caiying
• Is Part Of: Environmental toxicology. Volume 37:Issue 11(2022)
• Page Start: 2660
• Page End: 2672
• Publication Date: 2022-08-04
• Subjects: autophagy -- cadmium -- calcium homeostasis -- duck renal tubular epithelial cell -- PLC‐IP3‐IP3R pathway; Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.23626
• Languages: English
• ISSNs: 1520-4081

Abstract

Abstract: Cadmium (Cd) is detrimental to animals, but nephrotoxic effects of Cd on duck have not been fully elucidated. To evaluate the impacts of Cd on Ca homeostasis and autophagy via PLC‐IP3 ‐IP3 R pathway, primary duck renal tubular epithelial cells were exposed to 2.5 μM and 5.0 μM Cd, and combination of 5.0 μM Cd and 10.0 μM 2‐APB or 0.125 μM U‐73122 for 12 h (U‐73122 pretreated for 1 h). These results evidenced that Cd induced [Ca 2+ ]c overload mainly came from intracellular Ca store. Cd caused [Ca 2+ ]mit and [Ca 2+ ]c overload with [Ca 2+ ]ER decrease, elevated Ca homeostasis related factors (GRP78, GRP94, CRT, CaN, CaMKII, and CaMKKβ) expression, PLC and IP3 activities and IP3 R expression, but subcellular Ca 2+ redistribution was reversed by 2‐APB. PLC inhibitor U‐73122 dramatically relieved the changes of the above indicators induced by Cd. Additionally, U‐73122 obviously reduced the number of autophagosomes and LC3 accumulation spots, Atg5, LC3A, LC3B mRNA levels and LC3II/LC3I, Beclin‐1 protein levels induced by Cd, and markedly elevated p62 mRNA and protein levels. Overall, the results verified that Cd induced [Ca 2+ ]c overload mainly originated from ER Ca 2+ release mediated by PLC‐IP3 ‐IP3 R pathway, then triggered autophagy in duck renal tubular epithelial cells.