Oxidative stress and gene expression in sepsis

Macdonald, Jamie; Galley, Helen F.; Webster, Nigel R.

doi:10.1093/bja/aeg034

Cited by 445 publications

(319 citation statements)

References 105 publications

(86 reference statements)

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“…Similarly in the Adriamycin model of renal failure, renal cortex GPx activity was decreased to 69% of the control levels at 20 weeks after Adriamycin treatment Van den Branden et al (2000). These results also are in a harmony with the recorded data by Macdonald et al (2003) explained the oxidative stress occurs when a balance is disrupted by excessive production of Reactive Oxygen Speacies (ROS), including superoxide, hydrogen peroxide and hydroxyl radicals and/or by inadequate antioxidant defenses, including suboptimal levels of catalase, Glutathione Peroxidase (GPx), vitamins C and E and reduced glutathion. Sener et al (2004) found that in the erythrocytes of male Wistar albino rats at 4 weeks after 5/6 nephrectomy, GPx activity was found to be reduced, in addition Devinder et al (2004) found that the glycerol treated group showed depletion in antioxidant system which indicated by the significant decrease in the levels of glutathione reductase and superoxide dismutase enzymes.…”

Section: Discussionsupporting

confidence: 77%

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Elgendey¹,

Hemeda²,

Sosa³

et al. 2015

American Journal of Biochemistry and Biotechnology

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Acute Renal Failure (ARF) has traditionally been defined as the abrupt and progressive loss of kidney functions resulting in the retention of urea and other nitrogenous waste products associated with interstitial inflammation, tubular injury and increasing Tumor Necrosis Factor (TNF). Mortality in patients with ARF remains high >50% in severely ill patients. Klotho gene is a new anti-aging gene. Genetic mutation of klotho gene causes multiple premature aging-like phenotypes and shortens lifespan. Klotho gene is highly expressed in the kidney and a soluble form of klotho functions as an endocrine substance that exerts multiple actions including the modulation of renal solute transport and the protection of the kidney. This study aimed to clarify the pre treatment and/or post treatment effect of vitamin E as an antioxidant on kidney functions, klotho gene expression and glutathione peroxidase-1 gene expression among rats with acute renal failure. Using glycerol as oxidative stress factor to cause acute renal failure and Real time PCR for assessment of gene expression of target gene in the control and treated groups. Our results demonstrated that the vitamin E (α tocopherol) as antioxidant factor decreased the kidney injuries as pre renal failure administer and improve kidney function as post renal failure administer. Those effects were through up regulating the Klotho as anti aging gene and the Glutathione Peroxidase (GPx-1) as antioxidant gene expression in the kidney tissue. We concluded that factors those up regulate the klotho gene expression can use as protective factors against kidney injuries and to improve kidney function in renal failure.

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Section: Discussionsupporting

confidence: 77%

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Elgendey¹,

Hemeda²,

Sosa³

et al. 2015

American Journal of Biochemistry and Biotechnology

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“…SOD is a metallo-enzyme that catalyzes the dismutation of the superoxide anion (from oxidative phosphorylation, in ammation processes, ischemia, phagocytosis and in response to LPS and cytokines) to H2O2 [43]. is H 2 O 2 is later metabolized into water by glutathione peroxidase and catalase.…”

Section: Superoxide Dismutase (Sod)mentioning

confidence: 99%

Sepsis, mitochondrial failure and multiple organ dysfunction

Dúran-Bedolla

Oca-Sandoval²,

Saldaña-Navor³

et al. 2014

CIM

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Purpose: e purpose of this review is to consider the state of oxidative stress, failure of the antioxidant systems and mitochondrial failure as the main physiopathological mechanisms leading to multiple organ dysfunction during sepsis.Principal ndings: Sepsis is a clinical syndrome caused by a severe infection that triggers an exaggerated in ammatory response. Involved in the pathogenesis of sepsis are the activation of in ammatory, immune, hormonal, metabolic and bioenergetic responses. One of the pivotal factors in these processes is the increase of reactive species accompanied by the failure of the antioxidant systems, leading to a state of irreversible oxidative stress and mitochondrial failure.In a physiological state, reactive species and antioxidant systems are in redox balance. e loss of this balance during both chronic and infectious diseases leads to a state of oxidative stress, which is considered to be the greatest promoter of a systemic in ammatory response.e loss of the redox balance, together with a systemic in ammatory response during sepsis, can lead to progressive and irreversible mitochondrial failure, energy depletion, hypoxia, septic shock, severe sepsis, multiple organ dysfunction and death of the patient. Conclusion:Knowledge of the molecular processes associated with the development of oxidative stress should facilitate the development of e ective therapies and better prognosis for patients with sepsis and organ dysfunction.

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“…Increased production of ROS accompanies inflammatory conditions, such as ischemiareperfusion injury and sepsis, and appears to contribute to organ system dysfunction in these settings (25,26). H 2 O 2 rapidly transits across cell membranes, and incubation of neutrophils and other cell populations with H 2 O 2 or the H 2 O 2 generating combination of glucose and glucose oxidase results in increased intracellular concentrations of H 2 O 2 , diminished 26 S proteasomal activity, and stabilization of cytoplasmic levels of proteins, such as IB-␣, that are normally degraded by the 26 S proteasome (27)(28)(29).…”

mentioning

confidence: 99%

S-Glutathionylation of the Rpn2 Regulatory Subunit Inhibits 26 S Proteasomal Function

Żmijewski

Banerjee²,

Abraham

2009

Journal of Biological Chemistry

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Although increased intracellular concentrations of hydrogen peroxide (H 2 O 2 ) are associated with inhibition of 26 S proteasomal activity, the mechanisms responsible for such effects have not been well delineated. In the present studies, we found that direct exposure of purified 26 S proteasomes to H 2 O 2 had negligible effects on their activity, whereas incubation with glutathione and H 2 O 2 produced >80% decrease in chymotrypsin-like and trypsin-like activities. Rpn1 and Rpn2, which are subunits of the 19 S regulatory particle, undergo S-glutathionylation after exposure of purified 26 S proteasomes to glutathione and H 2 O 2 , as well as in HEK 293 cells and neutrophils incubated with H 2 O 2 . Increased oxidation of Rpn1 and Rpn2 cysteine thiols was also found in lung extracts from mice in which catalase was inactivated, a condition associated with augmented intracellular concentrations of H 2 O 2 and diminished 26 S proteasomal activity. Although unoxidized Rpn2 enhanced 20 S proteolytic function in vitro, such potentiation was not found when the 20 S core particle was incubated with oxidized Rpn2. The composition of 26 S proteasomes was not altered after exposure to glutathione and H 2 O 2 , with similar amounts of Rpn1 and Rpn2 in control or oxidized 26 S proteasomal complexes. These findings identify S-glutathionylation of Rpn2 as a contributory mechanism for H 2 O 2 -induced inhibition of 26 S proteasomal function.The ubiquitin-proteasomal system is a major pathway for protein degradation and is involved in multiple cellular processes, including cell cycle control, expression of cell surface receptors, and regulation of intracellular levels of structural and regulatory proteins and transcription factors (1-6). The 26 S proteasome is composed of two main components, a proteolytic 20 S core particle (CP) 2 and an ATPase containing 19 S regulatory particle (RP) (7-10). Ubiquitinated proteins are unfolded in the 19 S RP and then translocated into the 20 S CP where they are degraded. The 20 S CP is composed of four heptameric rings of ␣ and ␤ subunits, with the two inner ␤ rings having proteolytic activity. The 19 S RP consists of a lid and base subcomplex, with the base subcomplex, including the nonenzymatic Rpn1 and Rpn2 toroids, surrounded by six AAA-type ATPases. Rpn1 and Rpn2 appear to play a major regulatory role by modulating the translocation and subsequent degradation of ubiquitinated substrates in the proteolytic core of the 20 S CP (7,(11)(12)(13)(14)(15).Decreased 26 S proteasomal activity, resulting in the accumulation of intracellular proteins, has been associated with aging (16, 17) and with pathophysiologic processes, including heart failure, neurodegenerative diseases, and alcohol induced liver injury (18 -20). A number of recent studies have shown that time-limited inhibition of the 26 S proteasome is beneficial as a therapeutic intervention for malignancies, such as multiple myeloma, and in reducing inflammation and cell injury associated with ischemia-reperfusion injury and transplanta...

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Oxidative stress and gene expression in sepsis

Cited by 445 publications

References 105 publications

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Sepsis, mitochondrial failure and multiple organ dysfunction

S-Glutathionylation of the Rpn2 Regulatory Subunit Inhibits 26 S Proteasomal Function

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