Differential protein expression in metallothionein protection from depleted uranium-induced nephrotoxicity
نویسندگان
چکیده
The purpose of this study was to investigate the underlying mechanism of metallothionein (MT) protection from depleted uranium (DU) using a proteomics approach to search for a DU toxicity-differential protein. MT-/- and MT+/+ mice were administrated with a single dose of DU (10 mg/kg, i.p.) or equal volume of saline. After 4 days, protein changes in kidney tissues were evaluated using a proteomics approach. A total of 13 differentially expressed proteins were identified using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The validating results showed that the expression of aminoacylase-3 (ACY-3) and the mitochondrial ethylmalonic encephalopathy 1 (ETHE1) decreased significantly after DU exposure; in addition, the reduction in MT-/- mice was more significant than that in MT+/+ mice. The results also showed that exogenous ETHE1 or ACY-3 could increase the survival rate of human embryonic kidney 293 (HEK293) cells after DU exposure. A specific siRNA of ETHE1 significantly increased cell apoptosis rates after DU exposure, whereas exogenous ETHE1 significantly decreased cell apoptosis rates. In summary, ACY-3 and ETHE1 might involve in protection roles of MT. ETHE1 could be a new sensitive molecular target of DU-induced cell apoptosis.
منابع مشابه
Mitochondrial Toxicity of Depleted Uranium: Protection by Beta-Glucan
Considerable evidence suggests that mitochondrial dysfunction contributes to the toxicity of uranyl acetate (UA), a soluble salt of depleted uranium (DU). We examined the ability of the two antioxidants, beta-glucan and butylated hydroxyl toluene (BHT), to prevent UA-induced mitochondrial dysfunction using rat-isolated kidney mitochondria. Beta-glucan (150 nM) and BHT (20 nM) attenuated UA-indu...
متن کاملMitochondrial Toxicity of Depleted Uranium: Protection by Beta-Glucan
Considerable evidence suggests that mitochondrial dysfunction contributes to the toxicity of uranyl acetate (UA), a soluble salt of depleted uranium (DU). We examined the ability of the two antioxidants, beta-glucan and butylated hydroxyl toluene (BHT), to prevent UA-induced mitochondrial dysfunction using rat-isolated kidney mitochondria. Beta-glucan (150 nM) and BHT (20 nM) attenuated UA-indu...
متن کاملMitochondrial Toxicity of Depleted Uranium: Protection by Beta-Glucan
Considerable evidence suggests that mitochondrial dysfunction contributes to the toxicity of uranyl acetate (UA), a soluble salt of depleted uranium (DU). We examined the ability of the two antioxidants, beta-glucan and butylated hydroxyl toluene (BHT), to prevent UA-induced mitochondrial dysfunction using rat-isolated kidney mitochondria. Beta-glucan (150 nM) and BHT (20 nM) attenuated UA-indu...
متن کاملToxicity of depleted uranium on isolated rat kidney mitochondria.
BACKGROUND Kidney is known as the most sensitive target organ for depleted uranium (DU) toxicity in comparison to other organs. Although the oxidative stress and mitochondrial damage induced by DU has been well investigated, the precise mechanism of DU-induced nephrotoxicity has not been thoroughly recognized yet. METHODS Kidney mitochondria were obtained using differential centrifugation fro...
متن کاملDifferential Responses of Groel and Metallothionein Genes to Divalent Metal Cations and the Oxyanions of Arsenic in the Cyanobacterium Synechococcus Sp. Strain Pcc7942
A better understanding of the resistance mechanisms used by the cyanobacterium Synechococcus sp. PCC 7942 could guide attempts to develop this organism for use in bioremediation. This bacterium exhibits extraordinary resistance to arsenate. Possible mechanisms include exclusion from the cell, intraand extra-cellular binding, and potential interactions with proteins such as metallothioneins, whi...
متن کامل