Genetic overexpressing of <scp>GP</scp>x‐1 attenuates cocaine‐induced renal toxicity via induction of anti‐apoptotic factors

Nhu, Huynh; Jeong, Ji Hoon; Kim, Dae-Joong; Chung, Yoon Hee; Shin, Eun‐Joo; Nguyen, Lan Thuy Ty; Nam, Yunsung; Lee, Yu Jeung; Cho, Eunhee; Nah, Seung-Yeol; Jang, Choon‐Gon; Lei, Xin Gen; Kim, Hyoung‐Chun

doi:10.1111/1440-1681.12557

Cited by 15 publications

(6 citation statements)

References 45 publications

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“…An increase in the activity of caspase‐3 has also been well‐documented in cocaine‐treated hepatocytes (Zaragoza et al, ), suggesting that caspase‐3 is a downstream effector molecule of PKCδ and cytochrome c . Furthermore, we report for the first time here that genetic deletion of GPx‐1 potentiated cocaine‐induced mitochondrial translocation of cleaved PKCδ, cytochrome c release to the cytosol and activated caspase‐3 expression (Crack et al, ), whereas genetic overexpression of GPx‐1 attenuated PKCδ cleavage and mitochondrial translocation, which may further suppress downstream signaling (i.e., cytochrome c release and caspase‐3 activation) (Mai, Jeong, et al, ). In agreement, rottlerin, a PKCδ inhibitor, diminishes caspase‐3 activity in hepatocytes (Das, Ghosh, Manna, & Sil, ).…”

Section: Discussionmentioning

confidence: 93%

“…We recently demonstrated that protective attributes of GPx‐1 against psychostimulant‐induced oxidative stress are via activation of Nrf2‐dependent GSH synthetic system (Tran et al, ). We also demonstrated that GPx‐1 plays a protective role in response to cocaine‐induced renal toxicity by enhancing the expression of anti‐apoptotic proteins and reducing the expression of pro‐apoptotic proteins (Mai et al, ).…”

Section: Introductionmentioning

confidence: 82%

“…Breeding pairs of GPx‐1 TG mice were kindly provided by Professor Xin Gen Lei (Cornell University, Ithaca, NY, USA). Polymerase chain reaction primers for genotyping were as follows: 5′‐CCT ACA TTT TGA ATG GAA GGA TTG GAG CTA GGG G‐3′ and 5′‐CTC AAA CAA TGT AAA ATT GGG CTC GAA CCC GC‐3′ for KO mutant detection, and 5′‐CTC AAA CAA TGT AAA ATT GGG CTC GAA CCC GC‐3′ and 5′‐GAA AGC GAT GCC ACG TGA TCT CAG CAC CAT CC‐3′ for overexpressing TG detection (Bioneer Corporation, Daejeon, Republic of Korea) (Mai, Jeong, et al, ; Tran et al, ).…”

Section: Methodsmentioning

confidence: 99%

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Protective potential of glutathione peroxidase‐1 gene against cocaine‐induced acute hepatotoxic consequences in mice

Nhu

Jung

Kim

et al. 2018

J of Applied Toxicology

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Since the cocaine-induced oxidative stress has been established to lead to hepatotoxicity, we examined the role of the glutathione peroxidase (GPx)-1 gene in cocaine-induced hepatotoxicity. Cocaine treatment significantly increased superoxide dismutase activity in as little as 1 hour, with a maximum level at 6 hours in wild-type mice, while significantly decreasing GPx activity and subsequently inducing oxidative damage (i.e., reactive oxygen species, lipid peroxidation and protein carbonylation). These changes were more prominent in the mitochondrial fraction than in the cytosolic fraction. In contrast, genetic overexpression of GPx-1 significantly attenuated cocaine-induced oxidative damage in mice. Cocaine treatment significantly increased alanine aminotransferase and aspartate aminotransferase levels in the serum. Consistently, cocaine significantly enhanced cleaved caspase-3 expression and intramitochondrial Ca , while significantly reducing mitochondrial transmembrane potential. Cocaine treatment potentiated cleavage of protein kinase C δ (PKCδ), mitochondrial translocation of PKCδ, cytosolic release of cytochrome c and activation of caspase-3, followed by hepatopathologic changes. These results were more prominent in GPx-1 knockout than in wild-type mice, and they were less pronounced in overexpressing transgenic than in non-transgenic mice. Combined, our results suggest that the GPx-1 gene possesses protective potential against mitochondrial oxidative burden, mitochondrial dysfunction and hepatic degeneration induced by cocaine and that the protective mechanisms are associated with anti-apoptotic activity via inactivation of PKCδ.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

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Protective potential of glutathione peroxidase‐1 gene against cocaine‐induced acute hepatotoxic consequences in mice

Nhu

Jung

Kim

et al. 2018

J of Applied Toxicology

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“…Valencia et al reported that the presence of the ovary prevents hepatic mitochondrial oxidative stress in young and aged female mice through glutathione peroxidase 1 [ 29 ]. Mai et al found that genetic over-expression of GPX1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors [ 30 ]. In this study, the downregulated accumulation of GPX1 in mice fed an excessive selenium diet lowered the efficiency of ROS scavenging, which was associated with increased oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Protein Profile in Mice with Low or Excessive Selenium Diets

Wang

Zhang

et al. 2016

IJMS

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Dietary selenium putatively prevents oxidative damage, whereas excessive selenium may lead to animal disorder. In this study, we investigated the effects of low and excessive levels of dietary selenium on oxidative stress and mitochondrial proteins in mouse liver. Six to eight week old mice were fed a diet with low, excessive, or moderate (control) levels of selenium (sodium selenite). The selenium concentration and oxidative stress-related parameters in hepatic mitochondria were evaluated. Two-dimensional electrophoresis and mass spectrometry were applied to identify the differentially-expressed proteins associated with dietary selenium. The selenium content of the livers in mice with the low selenium diet was significantly lower than that of the control, while that of mice fed excessive levels was significantly higher. In both groups oxidative stress in hepatic mitochondria was found; accompanied by lower superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels and higher malondialdehyde (MDA) content, compared with the control group. Furthermore, ten proteins in the hepatic mitochondria of the selenium-low or -excessive groups with more than two-fold differences in abundance compared with the control group were identified. The differentially-expressed proteins in hepatic mitochondria may be associated with dietary (low or excessive) selenium-induced oxidative stress.

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“…The GPx‐1 TG mice were derived from B6C3 (C57BL/6 × C3H) hybrid mice, harbouring three copies of the GPx‐1 transgene . The mice were genotyped by polymerase chain reaction screening using genomic DNA isolated from each mouse tail using the following primers: 5′‐ CCT ACA TTT TGA ATG GAA GGA TTG GAG CTA GGG G‐3′ and 5′‐CTC AAA CAA TGT AAA ATT GGG CTC GAA CCC GC‐3′ for KO mutant detection, and 5′‐CTC AAA CAA TGT AAA ATT GGG CTC GAA CCC GC‐3′ and 5′‐GAA AGC GAT GCC ACG TGA TCT CAG CAC CAT CC‐3′ for overexpressing transgene detection (Bioneer Corporation, Daejeon, Republic of Korea) …”

Section: Methodsmentioning

confidence: 99%

Glutathione peroxidase‐1 gene rescues cocaine‐induced conditioned place preference in mice by inhibiting σ‐1 receptor expression

Pham

Chung

Nhu

et al. 2019

Clin Exp Pharma Physio

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The aim of this study was to investigate whether the glutathione peroxidase‐1 gene (GPx‐1) affects cocaine‐induced conditioned place preference (CPP) using a mouse model. Cocaine‐induced CPP was accompanied by an increase in the level of σ‐1 receptor in the nucleus accumbens (NAc). This phenomenon was more pronounced in the GPx‐1 gene knockout (GPx‐1 KO) than in wild type (WT) mice. In contrast, the CPP and expression of σ‐1 receptor were much less pronounced in GPx‐1‐overexpressing transgenic (GPx‐1 TG) mice than non‐transgenic (non‐TG) mice. Treatment of the mice with , a σ‐1 receptor antagonist, significantly attenuated both cocaine‐induced CPP and c‐Fos‐immunoreactivity (c‐Fos‐IR) in WT and GPx‐1 KO mice, although the effects were more evident in the latter group. Despite the protective effects of on cocaine‐induced CPP and c‐Fos in non‐TG mice, there were no additional protective effects in cocaine‐treated GPx‐1 TG mice, indicating that the σ‐1 receptor is a critical target for GPx‐1‐mediated psychoprotective activity. Overall, our results suggest that GPx‐1 attenuates cocaine‐induced CPP via inhibition of σ‐1 receptor expression.

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Genetic overexpressing of GPx‐1 attenuates cocaine‐induced renal toxicity via induction of anti‐apoptotic factors

Cited by 15 publications

References 45 publications

Protective potential of glutathione peroxidase‐1 gene against cocaine‐induced acute hepatotoxic consequences in mice

Protective potential of glutathione peroxidase‐1 gene against cocaine‐induced acute hepatotoxic consequences in mice

Mitochondrial Protein Profile in Mice with Low or Excessive Selenium Diets

Glutathione peroxidase‐1 gene rescues cocaine‐induced conditioned place preference in mice by inhibiting σ‐1 receptor expression

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