Tumour necrosis factor α induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor κB and activator protein-1

Yang, Heping; Magilnick, Nathaniel; Ou, Xiaopeng; Lu, Shelly C.

doi:10.1042/bj20050795

Cited by 73 publications

(97 citation statements)

References 42 publications

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“…Fibroblast cells derived from Nrf1 and Nrf2 knockout mice have lower GSH levels and reduced basal expression of GCLM (Kwong et al, 1999;Yang et al, 2005a). The rat GCLM promoter also has a functional ARE element (−295 to −285) (Yang et al, 2005b). This ARE element is important for basal promoter activity as well as TNFα-mediated induction of rat GCLM (Yang et al, 2005).…”

Section: Regulation Of Gcl Modifier Subunit (Gclm)-mentioning

confidence: 99%

“…Although the two GCL subunits are coordinately up-regulated by many inducers of oxidative stress and treatment with antioxidants (Galloway et al, 1997;Galloway et al, 1998;Moinova and Mulcahy, 1998;Moinova and Mulcahy, 1999;Wild et al, 1999, Erickson et al, 2002Yang et al, 2005b;Zheng et al, 2007), there are also examples where the two subunits of GCL are differentially regulated. Gipp et al found no correlation between the steady state mRNA levels of the two GCL subunits (Gipp et al, 1995).…”

Section: Regulation Of Gcl Modifier Subunit (Gclm)-mentioning

confidence: 99%

“…The 5′-flanking regions of human, rat, and mouse GCL subunits have all been cloned (Mulcahy and Gipp, 1995b;Mulcahy et al, 1997;Galloway et al, 1997;Moinova and Mulcahy, 1998;Hudson and Kavanagh, 2000;Yang et al, 2001;Solis et al, 2002;Yang et al, 2005b). Consensus NFκB, Sp-1, AP-1, activator protein-2 (AP-2), metal response (MRE), and antioxidant response (ARE)/electrophile responsive (EpRE) elements have been identified in the human GCLC promoter.…”

Section: Transcriptional Regulation Of Gclcmentioning

confidence: 99%

“…The explanation for these discrepant results is unclear and may reflect species and/or cell type differences in mediating the effect of these agents on GCLC promoter. Our recent study using the rat GCLC promoter revealed that NFκB is important in maintaining the basal expression of GCLC and in mediating the effect of TNFα-mediated induction of GCLC in rat hepatocytes (Yang et al, 2005b). NFκB can act on a consensus element present at −378 of the rat GCLC gene as well as induce the expression of AP-1 family member c-Jun to trans-activate AP-1 sites (Yang et al, 2005b).…”

Section: Transcriptional Regulation Of Gclcmentioning

confidence: 99%

“…Our recent study using the rat GCLC promoter revealed that NFκB is important in maintaining the basal expression of GCLC and in mediating the effect of TNFα-mediated induction of GCLC in rat hepatocytes (Yang et al, 2005b). NFκB can act on a consensus element present at −378 of the rat GCLC gene as well as induce the expression of AP-1 family member c-Jun to trans-activate AP-1 sites (Yang et al, 2005b). Thus, by acting directly and indirectly via inducing AP-1, NFκB is important in the expression of rat GCLC and perhaps human GCLC as well.…”

Section: Transcriptional Regulation Of Gclcmentioning

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: Regulation Of Gcl Modifier Subunit (Gclm)-mentioning

confidence: 99%

Section: Regulation Of Gcl Modifier Subunit (Gclm)-mentioning

confidence: 99%

Section: Transcriptional Regulation Of Gclcmentioning

confidence: 99%

Section: Transcriptional Regulation Of Gclcmentioning

confidence: 99%

Section: Transcriptional Regulation Of Gclcmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of glutathione synthesis

Lu¹

2009

Molecular Aspects of Medicine

1,604

765

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The association between ferroptosis and autophagy in cardiovascular diseases

Zhang,

Yang,

Ouyang

et al. 2024

Cell Biochemistry & Function

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Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron‐dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases.

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Dysregulation of glutathione synthesis during cholestasis in mice: Molecular mechanisms and therapeutic implications

Yang¹,

Ramani²,

Xia³

et al. 2009

Hepatology

Self Cite

110

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Glutathione (GSH) provides important antioxidant defense and regulates multiple critical processes including fibrogenesis. There are conflicting literature studies regarding changes in GSH during cholestasis. Here we examined changes in the GSH synthetic enzymes during bile duct ligation (BDL) in mice and how treatment with ursodeoxycholic acid (UDCA) and/or S-adenosylmethionine (SAMe) affects the expression of these enzymes and liver injury. The hepatic expression of glutamate-cysteine ligase (GCL) subunits and GSH synthase (GS) increased transiently after BDL but fell to 50% of baseline by 2 weeks. Nuclear factor-erythroid 2-related factor 2 (Nrf2) trans-activates gene expression by way of the antioxidant response element (ARE), which controls the expression of all three genes. Despite increased Nrf2 nuclear levels, Nrf2 nuclear binding to ARE fell 2 weeks after BDL. Nuclear levels of c-Maf and MafG, which can negatively regulate ARE, were persistently induced during BDL and the dominant proteins bound to ARE on day 14. UDCA and SAMe induced the expression of GCL subunits and raised GSH levels. They increased nuclear Nrf2 levels, prevented c-Maf and MafG induction, and prevented the fall in Nrf2 nuclear binding to ARE. Combined treatment had additive effects, reduced liver cell death, and prevented fibrosis. Conclusion: GSH synthesis falls during later stages of BDL due to lower expression of GSH synthetic enzymes. UDCA and SAMe treatment prevented this fall and combined therapy was more effective on preserving GSH levels and preventing liver injury. (HEPATOLOGY 2009;49:1982-1991

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Tumour necrosis factor α induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor κB and activator protein-1

Cited by 73 publications

References 42 publications

Regulation of glutathione synthesis

Regulation of glutathione synthesis

The association between ferroptosis and autophagy in cardiovascular diseases

Dysregulation of glutathione synthesis during cholestasis in mice: Molecular mechanisms and therapeutic implications

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