Lead inhibits in vitro creatine kinase and pyruvate kinase activity in brain cortex of rats

Lepper, Tatiana Wannmacher; Oliveira, Evandro; Koch, Gustavo Duarte Waltereith; Berlese, Daiane Bolzan; Feksa, Luciane Rosa

doi:10.1016/j.tiv.2009.11.012

Cited by 32 publications

(15 citation statements)

References 62 publications

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“…In any biological system where ROS production increases, antioxidant reserves are depleted. One of the effects of Pb exposure impacts GSH metabolism (Lepper et al 2010).…”

Section: Resultsmentioning

confidence: 99%

“…This is manifested by alterations to several hematological parameters, such as HGB, HCT, RBC, and MCV, which were lower in Pb-exposed individuals than in controls. If inhibition of thiol-containing enzymes does take place in patients subject to occupational Pb exposure, then increasing the thiol/disulfide ratio by administering GSH could be an important tool to prevent some of the metabolic consequences of Pb exposure (Lepper et al 2010). However, further studies that evaluate the activity of thiol-containing enzymes, such as PK and d-ALAD, in occupationally Pb-exposed workers are still needed.…”

Section: Resultsmentioning

confidence: 99%

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Pyruvate Kinase Activity and δ-Aminolevulinic Acid Dehydratase Activity as Biomarkers of Toxicity in Workers Exposed to Lead

Feksa

Oliveira

Trombini

et al. 2012

Arch Environ Contam Toxicol

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Lead (Pb(2+)) is a heavy metal that has long been used by humans for a wide range of technological purposes, which is the main reason for its current widespread distribution. Pb(2+) is thought to enter erythrocytes through anion exchange and to remain in the cell by binding to thiol groups. Pyruvate kinase (PK) is a thiol-containing enzyme that plays a key role in erythrocyte cellular energy homeostasis. δ-aminolevulinic acid dehydratase (δ-ALAD) is the second enzyme in the heme biosynthetic pathway and plays a role in the pathogenesis of Pb poisoning. Our primary objective was to investigate the effect of Pb(2+) on the activity of the thiolenzymes δ-ALAD and PK and on the concentration of glutathione (GSH), a nonenzymatic antioxidant defense, in erythrocytes from Pb-exposed workers. The study sample comprised 22 male Pb workers and 21 normal volunteers (15 men and 6 women). The Pb-exposed workers were employed in manufacturing and recycling of automotive batteries. Basic red-cell parameters were assayed and total white blood cell counts performed. PK and δ-ALAD activity and blood Pb (BPb) concentrations were determined in all subjects. Pb-exposed individuals had significantly greater BPb levels than controls. Both PK and δ-ALAD activity levels were significantly lower in Pb-exposed individuals than in controls. Pb significantly inhibited PK and δ-ALAD activity in a dose-dependent manner. We found that erythrocyte GSH levels were lower in Pb-exposed individuals than normal volunteers. Pb-exposed individuals had lower values than controls for several red cell parameters (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume). These results suggest that Pb inhibits δ-ALAD and PK activity by interacting with their thiol groups. It is therefore possible that Pb disrupts energy homeostasis and may be linked with decreased glucose metabolism because it affects the heme synthesis pathway in erythrocytes, contributing to the cell dysfunction observed in these in Pb-exposed individuals. These results indicate an apparent dose-effect relationship between PK activity and BPb. PK activity in human erythrocytes can be used for biological monitoring of Pb exposure. Study of the mechanisms by which Pb acts may contribute to greater understanding of the symptoms caused by Pb.

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“…In any biological system where ROS production increases, antioxidant reserves are depleted. One of the effects of Pb exposure impacts GSH metabolism (Lepper et al 2010).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Pyruvate Kinase Activity and δ-Aminolevulinic Acid Dehydratase Activity as Biomarkers of Toxicity in Workers Exposed to Lead

Feksa

Oliveira

Trombini

et al. 2012

Arch Environ Contam Toxicol

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“…Frozen samples were pulverized in liquid N 2 , and about 100 mg of each sample were used to measure pyruvate kinase (PK) activity according to Lepper et al (2010) with some modification. The samples were extracted with 3 mL 100 mM Tris-HCl (pH 7.5) containing 10 mM β-mercaptoethanol, 12.5% (v/v) glycerine, l mM EDTA-Na 2 , 10 mM MgCl 2 , and 1% (m/v) PVP-40.…”

Section: Methodsmentioning

confidence: 99%

NRT1.1-dependent NH4+ toxicity in Arabidopsis is associated with disturbed balance between NH4+ uptake and assimilation

Jian

Liao

Song

et al. 2017

Preprint

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“…PK has a key role for energy homeostasis in brain tissues [203]. It has been revealed that the increasing activity of pyruvate kinase was followed by enhancement of glucose-dependence of brains in aged rats [204].…”

Section: Oxidation Protein-adductsmentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in aging and cancer

et al. 2016

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Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.

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Lead inhibits in vitro creatine kinase and pyruvate kinase activity in brain cortex of rats

Cited by 32 publications

References 62 publications

Pyruvate Kinase Activity and δ-Aminolevulinic Acid Dehydratase Activity as Biomarkers of Toxicity in Workers Exposed to Lead

Pyruvate Kinase Activity and δ-Aminolevulinic Acid Dehydratase Activity as Biomarkers of Toxicity in Workers Exposed to Lead

NRT1.1-dependent NH4+ toxicity in Arabidopsis is associated with disturbed balance between NH4+ uptake and assimilation

Mitochondrial dysfunction and oxidative stress in aging and cancer

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