Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents

Chu, Fong‐Fong; Esworthy, R. Steven; Doroshow, James H.; Doan, K; Liu, Xian‐Fang

doi:10.1182/blood.v79.12.3233.3233

Cited by 41 publications

(11 citation statements)

References 20 publications

(2 reference statements)

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“…Similarly, eGPx serves an important antioxidant role in many other extracellular surfaces and spaces (9, 30 -36). Specifically, eGPx transcripts have been demonstrated in epithelial cells with well-developed brush borders, e.g., visceral yolk sac, the intestine, and the S1 and S2 segments of the renal tubules (9,10,31). The human airway epithelium expresses and secretes eGPx into the apical surface lining fluid (9).…”

Section: Discussionmentioning

confidence: 99%

Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells

et al. 2001

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A critical first-line antioxidant defense on the airway epithelial surface against reactive oxygen and nitrogen species (ROS and RNS) is extracellular glutathione peroxidase (eGPx). Little is known about the regulation of eGPx or its role in ROS-mediated lung diseases such as asthma. Here we show that eGPx is increased in the asthmatic airway in comparison to healthy controls. Higher levels of eGPx mRNA in asthmatic airway epithelium verified bronchial epithelial cells as the source for the increased eGPx. The eGPx mRNA in bronchial epithelial cells in vitro increased eightfold after exposure to ROS and glutathione, an essential cofactor for eGPx activity. Alterations in intracellular and extracellular oxidized and reduced glutathione were temporally associated with eGPx induction, further supporting redox mechanisms in gene expression. Overexpression of superoxide dismutase, but not catalase, inhibited induction and identified superoxide as a key intermediary. The eGPx mRNA half-life was not affected by ROS, suggesting a transcriptional mechanism for eGPx regulation. Fusion genes of deletion fragments of the eGPx gene 5' flanking region driving a reporter gene conclusively identified the ROS-responsive region, which contained the consensus DNA binding site for the redox-regulated transcription factor, activator protein 1.

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Section: Discussionmentioning

confidence: 99%

Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells

et al. 2001

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“…Glutathione peroxidase could play a major role in protecting mammals from the toxicity of ingested lipid peroxides. Plasma glutathione peroxidase as well as classical cellular glutathione peroxidase is present in liver (22). Plasma glutathione peroxidase can reduce phospholipid hydroperoxides but cannot reduce cholesterol hydroperoxides (23).…”

Section: Discussionmentioning

confidence: 99%

Cholesterol‐derived hydroperoxides in alcoholic liver disease

Asano

Adachi

Ueno

1999

Lipids

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Human liver samples from 33 patients were collected at autopsy (controls, n = 9; fatty liver, n = 12; liver cirrhosis, n = 12), and samples homogenized. Lipids extracted with chloroform and methanol were injected into the octyl column of a high-performance liquid chromatograph with post-column chemiluminescence. Liquid chromatography-mass spectrometry was developed to identify 7-hydroperoxycholest-5-en-3 beta-ol (7-OOH). We found that two cholesterol-derived hydroperoxides, 7 alpha-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH) and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-OOH), are present in significantly elevated amounts (12.4 and 25.0 nmol/g tissue, respectively) in lipid extracts from alcoholic fatty liver, but not in extracts from alcoholic cirrhotic liver. 7 alpha-OOH and 7 beta-OOH are early intermediates produced during free radical-mediated cholesterol oxidation and can serve as molecular indicators of chain peroxidative damage in cell membranes. This is the first demonstration of 7 alpha-OOH and 7 beta-OOH accumulations in human liver, and it is presumed to reflect greater oxidative stress pathology in alcoholic fatty liver.

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“…It has been shown that in humans, plasma GSH-Px is synthesized primarily in the proximal tubular cells of the kidney (Avissar et al, 1994). Along with the kidney, this enzyme is also synthesized in the liver, lung, heart, breast, intestine, brain, skeletal muscle and placenta, from which it is secreted into the extracellular fluid (Chu et al, 1992;Avissar et al, 1994;Behne & Kyriakopoulos, 2001).…”

Section: Selenium and Glutathione Peroxidases In Patients With Chronimentioning

confidence: 99%

Red blood cell and plasma glutathione peroxidase activities and selenium concentration in patients with chronic kidney disease: a review.

Zachara

Gromadzińska²,

Wąsowicz³

et al. 2006

Acta Biochim Pol

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The metabolism of oxygen in aerobic organisms leads to generation of reactive oxygen species (ROS). These entities are able to oxidize almost all classes of macromolecules, including proteins, lipids and nucleic acids. The physiological level of ROS is usually regulated by antioxidant defense mechanisms. There are at least three groups of antioxidant enzymes: superoxide dismutases, catalases and glutathione peroxidases (GSH-Pxs) which neutralize ROS. The trace elements (copper, zinc and selenium) bound to the active sites of the above listed enzymes play an important role in the antioxidant defense system. In mammals, a major function of selenium (Se) and Se-dependent GSH-Pxs is to protect cells from oxidative stress. Selenium concentrations and GSH-Px activities are altered in blood components of chronic kidney disease (CKD) patients. The Se level is frequently lower than in healthy subjects and the concentration very often decreases gradually with advancing stage of the disease. Studies on red cell GSH-Px activity in CKD patients reported its values significantly lower, significantly higher and lower or higher, but not significantly as compared with healthy subjects. On the other hand, all authors who studied plasma GSH-Px activity have shown significantly lower values than in healthy subjects. The degree of the reduction decreases gradually with the progression of the disease. High inverse correlations were seen between plasma GSH-Px activity and creatinine level. A gradual decrease in plasma GSH-Px activity in CKD patients is due to the fact that this enzyme is synthesized predominantly in the kidney and thus the impairment of this organ is the cause of the enzyme's lower activity. Se supplementation to CKD patients has a slightly positive effect in the incipient stage of the disease, but usually no effect was observed in end-stage CKD. Presently, kidney transplantation is the only treatment that may restore plasma Se level and GSH-Px activity in patients suffering from end-stage CKD. A few studies have shown that in kidney recipients, plasma Se concentration and GSH-Px activity are restored to normal values within a period of 2 weeks to 3 months following surgery and thus it can be acknowledged that Se supplementation to those patients has a positive effect on plasma GSH-Px activity.

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Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents

Cited by 41 publications

References 20 publications

Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells

Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells

Cholesterol‐derived hydroperoxides in alcoholic liver disease

Red blood cell and plasma glutathione peroxidase activities and selenium concentration in patients with chronic kidney disease: a review.

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