TY - JOUR
T1 - Endoplasmic reticulum stress participates in the pathophysiology of mercury-caused acute kidney injury
AU - Rojas-Franco, Plácido
AU - Franco-Colín, Margarita
AU - Torres-Manzo, Alejandra Paola
AU - Blas-Valdivia, Vanessa
AU - Thompson-Bonilla, María del Rocio
AU - Kandir, Sinan
AU - Cano-Europa, Edgar
N1 - Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Acute exposure to mercury chloride (HgCl2) causes acute kidney injury (AKI). Some metals interfere with protein folding, leading to endoplasmic reticulum stress (ERS), and the activation of cell death mechanisms, but in the case of mercury, there is no knowledge about whether the ERS mediates tubular damage. This study aimed to determinate if HgCl2 causes an AKI course with temporary activation of ERS and if this mechanism is involved in kidney cell death. Male mice were intoxicated with 5 mg/kg HgCl2 and sacrificed after 24, 48, 72, and 96 h of mercury administration. The kidneys of euthanized mice were used to assess the renal function, oxidative stress, redox environment, antioxidant enzymatic system, cell death, and reticulum stress markers (PERK, ATF-6, and IRE1α pathways). The results indicate temporary-dependent renal dysfunction, oxidative stress, and an increase of glutathione-dependent enzymes involved in the bioaccumulation process of mercury, as well as the enhancement of caspase 3 activity along with IRE1a, GADD-153, and caspase 12 expressions. Mercury activates the PERK/eIF2α branch during the first 48 h. Meanwhile, the activation of PERK/ATF-4 branch allowed for ATF-4, ATF-6, and IRE1α pathways to enhance GADD-153. It led to the activation of caspases 12 and 3, which mediated the deaths of the tubular and glomerular cells. This study revealed temporary-dependent ERS present during AKI caused by HgCl2, as well as how it plays a pivotal role in kidney cell damage.
AB - Acute exposure to mercury chloride (HgCl2) causes acute kidney injury (AKI). Some metals interfere with protein folding, leading to endoplasmic reticulum stress (ERS), and the activation of cell death mechanisms, but in the case of mercury, there is no knowledge about whether the ERS mediates tubular damage. This study aimed to determinate if HgCl2 causes an AKI course with temporary activation of ERS and if this mechanism is involved in kidney cell death. Male mice were intoxicated with 5 mg/kg HgCl2 and sacrificed after 24, 48, 72, and 96 h of mercury administration. The kidneys of euthanized mice were used to assess the renal function, oxidative stress, redox environment, antioxidant enzymatic system, cell death, and reticulum stress markers (PERK, ATF-6, and IRE1α pathways). The results indicate temporary-dependent renal dysfunction, oxidative stress, and an increase of glutathione-dependent enzymes involved in the bioaccumulation process of mercury, as well as the enhancement of caspase 3 activity along with IRE1a, GADD-153, and caspase 12 expressions. Mercury activates the PERK/eIF2α branch during the first 48 h. Meanwhile, the activation of PERK/ATF-4 branch allowed for ATF-4, ATF-6, and IRE1α pathways to enhance GADD-153. It led to the activation of caspases 12 and 3, which mediated the deaths of the tubular and glomerular cells. This study revealed temporary-dependent ERS present during AKI caused by HgCl2, as well as how it plays a pivotal role in kidney cell damage.
KW - Mercury nephrotoxicity
KW - acute kidney injury
KW - endoplasmic reticulum stress
KW - mercury chloride
KW - unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=85075114481&partnerID=8YFLogxK
U2 - 10.1080/0886022X.2019.1686019
DO - 10.1080/0886022X.2019.1686019
M3 - Artículo
C2 - 31736398
AN - SCOPUS:85075114481
SN - 0886-022X
VL - 41
SP - 1001
EP - 1010
JO - Renal Failure
JF - Renal Failure
IS - 1
ER -