Nitric oxide modulates glutathione synthesis during endotoxemia

Payabvash, Seyedmehdi; Ghahremani, Mohammad Hossein; Goliaei, Ardeshir; Mandegary, Ali; Shafaroodi, Hamed; Amanlou, Massoud; Dehpour, Ahmad Reza

doi:10.1016/j.freeradbiomed.2006.09.010

Cited by 44 publications

(61 citation statements)

References 50 publications

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“…Also, treatment of rat aortic vascular smooth muscle cells with NO at physiological concentrations resulted in increased cell GSH level and expression of both GCL subunits (Moellering et al, 1998). These results appear to contradict finding reported in vivo (Payabvash et al, 2006). Suffice to say, the molecular mechanism of how GCL expression falls during endotoxemia and whether NO regulates GCL expression in vivo remain largely unknown.…”

Section: Endotoxemiamentioning

confidence: 61%

“…Endotoxemia is also believed to participate in the pathogenesis of many liver diseases including alcoholic liver disease and nonalcoholic steatohepatitis (Su, 2002;Yang et al, 1997). GSH is an important variable that determines susceptibility to LPS-induced liver injury (Payabvash et al, 2006;Sun et al, 2006). In animal models, endotoxemia is known to lower GSH levels in the liver (Jaeschke, 1992;Payabvash et al, 2006) and in peritoneal macrophages and lymphocytes (Victor and De La Fuente, 2003).…”

Section: Endotoxemiamentioning

confidence: 99%

“…GSH is an important variable that determines susceptibility to LPS-induced liver injury (Payabvash et al, 2006;Sun et al, 2006). In animal models, endotoxemia is known to lower GSH levels in the liver (Jaeschke, 1992;Payabvash et al, 2006) and in peritoneal macrophages and lymphocytes (Victor and De La Fuente, 2003). This occurs also in patients hospitalized for sepsis as lower blood GSH:GSSG ratios have been reported (Németh and Boda, 2001).…”

Section: Endotoxemiamentioning

confidence: 99%

“…Part of it is secondary to oxidative stress, which is well documented to occur during endotoxemia (Zhang et al, 2000). However, one study (Payabvash et al, 2006) showed that a major part of hepatic GSH depletion during endotoxemia is a fall in GCL activity, which as associated with a fall in GCLC mRNA level. In support for this is that a cysteine prodrug was unable to prevent the fall.…”

Section: Endotoxemiamentioning

confidence: 99%

“…In support for this is that a cysteine prodrug was unable to prevent the fall. On the other hand, nitric oxide (NO) inhibitor (both non-specific and iNOS specific) ameliorated the fall in GSH (Payabvash et al, 2006). This would suggest that hepatic GCLC expression is inhibited by an increased in NO level.…”

Section: Endotoxemiamentioning

confidence: 99%

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Regulation of glutathione synthesis

Lu¹

2009

Molecular Aspects of Medicine

1,604

765

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Glutathione (GSH) is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation. GSH is synthesized in the cytosol of all mammalian cells in a tightly regulated manner. The major determinants of GSH synthesis are the availability of cysteine, the sulfur amino acid precursor, and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). GCL is composed for a catalytic (GCLC) and modifier (GCLM) subunit and they are regulated at multiple levels and at times differentially. The second enzyme of GSH synthesis, GSH synthase (GS) is also regulated in a coordinated manner as GCL subunits and its up-regulation can further enhance the capacity of the cell to synthesize GSH. Oxidative stress is well known to induce the expression of GSH synthetic enzymes. Key transcription factors identified thus far include Nrf2/Nrf1 via the antioxidant response element (ARE), activator protein-1 (AP-1) and nuclear factor κ B (NFκB). Dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. Manipulation of the GSH synthetic capacity is an important target in the treatment of many of these disorders.

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Section: Endotoxemiamentioning

confidence: 61%

Section: Endotoxemiamentioning

confidence: 99%

Section: Endotoxemiamentioning

confidence: 99%

Section: Endotoxemiamentioning

confidence: 99%

Section: Endotoxemiamentioning

confidence: 99%

See 3 more Smart Citations

Regulation of glutathione synthesis

Lu¹

2009

Molecular Aspects of Medicine

1,604

765

View full text Add to dashboard Cite

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Microneedles loaded with glutathione‐scavenging composites for nitric oxide enhanced photodynamic therapy of melanoma

Jia

Yang

et al. 2022

Bioengineering & Transla Med

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Photodynamic therapy (PDT) represents an attractive promising route for melanoma treatment. However, its therapeutic efficacy is compromised by inefficient drug delivery and high glutathione (GSH) levels in cancer cells. To overcome these challenges, microneedles (MNs) system loaded with GSH‐scavenging nanocomposites was presented for nitric oxide (NO) enhanced PDT. The nanocomposites consisted of S ‐nitroso‐ N ‐acrylate penicillamine (SNAP; a NO donor) grafted fourth‐generation polyamide amine dendrimer (G 4 ) and chlorin e6 (Ce6). Upon local insertion of polyvinylpyrrolidone MNs, G 4 ‐SNAP/Ce6 composites were fast delivered and significantly amplified the therapeutic effects during PDT, via GSH depletion and reactive nitrogen species generation. Even with a single administration and low power light exposure, MNs with G 4 ‐SNAP/Ce6 effectively halt the tumor progression. The system demonstrated better cancer ablation efficacy than Ce6 alone toward melanoma. The strategy may inspire new ideas for future PDT‐related therapy for skin tumors.

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Lipopolysaccharide-induced radical formation in the striatum is abolished in Nox2 gp91phox-deficient mice

et al. 2009

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Encephalopathy associated with septic shock as well as psychiatric disorders can be caused by the central nervous formation of reactive oxygen species (ROS) associated with inflammation. The systemic application of lipopolysaccharide (LPS, 100 mug/kg i.p.) also serves as a model for major depression and results in enhanced inflammatory processes. which are characterized by the stimulation of microglia or macrophages that then impair normal brain function. The aim of the present study was to analyze the effect of peripherally applied LPS on the central nervous formation of ROS and IL-6 in wild-type mice and in mice lacking the NADPH oxidase Nox2 subunit gp91phox. Microdialysis was performed in the striatum of the mice. Central nervous ROS were detected by electron spin resonance spectroscopy using 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) as reactant, which was infused via a microdialysis probe. IL-6 was measured in microdialysis samples by an immunoassay. Finally, blood samples were taken by heart puncture to detect IL-6 in plasma. In the wild-type mice, LPS significantly increased the ROS formation in the striatum of wild-type mice and resulted in a significantly enhanced IL-6 production. In the mice lacking the NADPH oxidase Nox2 subunit gp91phox, LPS did not enhance ROS formation, while central IL-6 was significantly increased. IL-6 plasma values were enhanced in both types of mice. In conclusion, the gp91phox-containing NADPH oxidase complex is involved in the central nervous ROS formation after peripheral LPS stimulation and might be a pharmacological target in patients with septic shock.

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Nitric oxide modulates glutathione synthesis during endotoxemia

Cited by 44 publications

References 50 publications

Regulation of glutathione synthesis

Regulation of glutathione synthesis

Microneedles loaded with glutathione‐scavenging composites for nitric oxide enhanced photodynamic therapy of melanoma

Lipopolysaccharide-induced radical formation in the striatum is abolished in Nox2 gp91phox-deficient mice

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