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Cadmium exposure induces autophagy via PLC-IP 3 -IP 3 R signaling pathway in duck renal tubular epithelial cells.

Authors :
Guo H
Huang B
Cui T
Chu X
Pu W
Huang G
Xing C
Zhang C
Source :
Environmental toxicology [Environ Toxicol] 2022 Nov; Vol. 37 (11), pp. 2660-2672. Date of Electronic Publication: 2022 Aug 04.
Publication Year :
2022

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-IP <subscript>3</subscript> -IP <subscript>3</subscript> 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 <superscript>2+</superscript> ] <subscript>c</subscript> overload mainly came from intracellular Ca store. Cd caused [Ca <superscript>2+</superscript> ] <subscript>mit</subscript> and [Ca <superscript>2+</superscript> ] <subscript>c</subscript> overload with [Ca <superscript>2+</superscript> ] <subscript>ER</subscript> decrease, elevated Ca homeostasis related factors (GRP78, GRP94, CRT, CaN, CaMKII, and CaMKKβ) expression, PLC and IP <subscript>3</subscript> activities and IP <subscript>3</subscript> R expression, but subcellular Ca <superscript>2+</superscript> 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 <superscript>2+</superscript> ] <subscript>c</subscript> overload mainly originated from ER Ca <superscript>2+</superscript> release mediated by PLC-IP <subscript>3</subscript> -IP <subscript>3</subscript> R pathway, then triggered autophagy in duck renal tubular epithelial cells.<br /> (© 2022 Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1522-7278
Volume :
37
Issue :
11
Database :
MEDLINE
Journal :
Environmental toxicology
Publication Type :
Academic Journal
Accession number :
35926093
Full Text :
https://doi.org/10.1002/tox.23626