Role of PLC/IP 3 /IP 3 R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells
Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP /IP R axis, primary duck renal tubular epithelial cells were exposed to 480 μM and 960 μM Mo, and joint of 9...
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Veröffentlicht in: | Environmental toxicology 2024-01, Vol.39 (1), p.172-183 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP
/IP
R axis, primary duck renal tubular epithelial cells were exposed to 480 μM and 960 μM Mo, and joint of 960 μM Mo and 10 μM 2-APB or 0.125 μM U-73122 for 12 h (U-73122 pretreated for 1 h), respectively. The data revealed that the increment of [Ca
]
induced by Mo mainly originated from intracellular Ca storage. Mo exposure reduced [Ca
]
, elevated [Ca
]
, [Ca
]
, and the expression of Ca homeostasis-related factors (Calpain, CaN, CRT, GRP94, GRP78 and CaMKII). 2-APB could effectively reverse subcellular Ca
redistribution by inhibiting IP
R, which confirmed that [Ca
]
overload induced by Mo originated from ER. Additionally, PLC inhibitor U-73122 remarkably mitigated the change, and dramatically reduced the number of apoptotic cells, the expression of Bak-1, Bax, cleaved-Caspase-3/Caspase-3, and notably increased the expression of Bcl-xL, Bcl-2, and Bcl-2/Bax ratio. Overall, the results confirmed that the Ca
liberation of ER via PLC/IP
/IP
R axis was the main cause of [Ca
]
overload, and then stimulated apoptosis in duck renal tubular epithelial cells. |
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ISSN: | 1520-4081 1522-7278 |
DOI: | 10.1002/tox.23956 |