Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages

Zhang, Hongqiao; Liu, Honglei; Zhou, Lulu; Yuen, Jenay

doi:10.1016/j.freeradbiomed.2017.10.010

Cited by 22 publications

(11 citation statements)

References 53 publications

(53 reference statements)

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“…Ref. [ 50 , 51 ]). It has been shown previously that exposure of THP1 macrophages to HOCl decreased intracellular GSH within the first hour of treatment, which was followed by a rebound, which surpassed the initial basal levels of GSH by up to 4-fold after 24 h [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

2020

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Myeloperoxidase (MPO) is a vital component of the innate immune system, which produces the potent oxidant hypochlorous acid (HOCl) to kill invading pathogens. However, an overproduction of HOCl during chronic inflammatory conditions causes damage to host cells, which promotes disease, including atherosclerosis. As such, there is increasing interest in the use of thiocyanate (SCN − ) therapeutically to decrease inflammatory disease, as SCN − is the favoured substrate for MPO, and a potent competitive inhibitor of HOCl formation. Use of SCN − by MPO forms hypothiocyanous acid (HOSCN), which can be less damaging to mammalian cells. In this study, we examined the ability of SCN − to modulate damage to macrophages induced by HOCl, which is relevant to lesion formation in atherosclerosis. Addition of SCN − prevented HOCl-mediated cell death, altered the extent and nature of thiol oxidation and the phosphorylation of mitogen activated protein kinases. These changes were dependent on the concentration of SCN − and were observed in some cases, at a sub-stoichiometric ratio of SCN − : HOCl. Co-treatment with SCN − also modulated HOCl-induced perturbations in the expression of various antioxidant and inflammatory genes. In general, the data reflect the conversion of HOCl to HOSCN, which can induce reversible modifications that are repairable by cells. However, our data also highlight the ability of HOSCN to increase pro-inflammatory gene expression and cytokine/chemokine release, which may be relevant to the use of SCN − therapeutically in atherosclerosis. Overall, this study provides further insight into the cellular pathways by which SCN − could exert protective effects on supplementation to decrease the development of chronic inflammatory diseases, such as atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

2020

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“…We observed time-dependent increases in GSS mRNA and protein levels following LPS stimulation, which subsequently promoted increases in GSH level. This could be explained by the LPS-induced inflammatory response stimulating the production and activation of enzymes associated with GSH biosynthesis [49] . Compared with other enzymes related to GSH biosynthesis, GSS was more sensitive to inflammation or LPS stimulation.…”

Section: Discussionmentioning

confidence: 99%

γ-glutamylcysteine exhibits anti-inflammatory effects by increasing cellular glutathione level

Yang

Hang

et al. 2019

Redox Biology

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Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection and characterized by redox imbalance and severe oxidative stress. Glutathione (GSH) serves several vital functions, including scavenging free radicals and maintaining intracellular redox balance. Extracellular GSH is unable to be taken into the majority of human cells, and the GSH prodrug N-acetyl-l-cysteine (NAC) does not exhibit promising clinical effects. γ-glutamylcysteine (γ-GC), an intermediate dipeptide of the GSH-synthesis pathway and harboring anti-inflammatory properties, represents a relatively unexplored option for sepsis treatment. The anti-inflammatory efficiency of γ-GC and the associated molecular mechanism need to be explored. In vivo investigation showed that γ-GC reduced sepsis lethality and attenuated systemic inflammatory responses in mice, as well as inhibited lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), high-mobility group box 1 (HMGB1), and nitric oxide (NO) and the expression of inducible NO synthase and cyclooxygenase 2 in RAW264.7 cells. Moreover, both in vivo and in vitro experiments demonstrated that γ-GC exhibited better therapeutic effects against inflammation compared with N-acetyl-L-cysteine (NAC) and GSH. Mechanistically, γ-GC suppressed LPS-induced reactive oxygen species accumulation and GSH depletion. Inflammatory stimuli, such as LPS treatment, upregulated the expression of glutathione synthetase via activating nuclear factor-erythroid 2-related factor (Nrf2) and nuclear factor kappa B (NF-κB) pathways, thereby promoting synthesis of GSH from γ-GC. These findings suggested that γ-GC might represent a potential therapeutic agent for sepsis treatment.

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“…The activation of a macrophage respiratory burst in response to infection with COVID-19 can induce the onset of ROS production and inflict oxidative damage to the host's tissues. ROS contribute to the oxidative damage that persists at the chronic stage of infection and is involved in functional impairment of the various tissues [ 19 ]. ROS is considered to be involved in eliminating pathogens, but recent studies suggest that viral growth is stimulated in an oxidative environment.…”

Section: Introductionmentioning

confidence: 99%

The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19

Jain

Parsanathan

Levine

et al. 2020

Free Radical Biology and Medicine

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There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its ‘oxidative immune-metabolic’ physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.

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Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages

Cited by 22 publications

References 53 publications

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

γ-glutamylcysteine exhibits anti-inflammatory effects by increasing cellular glutathione level

The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19

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