l-Cysteine in vitro can restore cellular glutathione and inhibits the expression of cell adhesion molecules in G6PD-deficient monocytes

Parsanathan, Rajesh; Jain, Sushil K.

doi:10.1007/s00726-018-2559-x

Cited by 31 publications

(15 citation statements)

References 60 publications

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“…The NO values obtained in the study were in line with published findings utilizing unstimulated and LPS-activated U937 cells ( 50 – 52 ). Monocytic cells exhibited a substantial (more than 1.5-fold) concentration-dependent increase ( P < 0.05) in NO and iNOS production when treated with mCRP (Figures 4 A and 5 A), regardless of their activation state.…”

Section: Resultssupporting

confidence: 90%

The Effect of C-Reactive Protein Isoforms on Nitric Oxide Production by U937 Monocytes/Macrophages

et al. 2018

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Inflammation is regulated by many endogenous factors including estrogen, a steroid hormone that declines with increasing age, leading to excessive inflammation in the elderly. C-reactive protein (CRP) is an acute phase inflammatory protein that exists in two forms, native CRP (nCRP) and monomeric CRP (mCRP), which mediate distinct biological activities. It is unclear how each CRP isoform mediates nitric oxide (NO), a signaling molecule generated by NO synthase (NOS). This study investigated whether CRP isoforms have distinct effects on NO production by unstimulated and lipopolysaccharide (LPS)-activated monocytes/macrophages and whether estrogen mediates CRP-induced NO production in an in vitro model of aging. NO and inducible NOS (iNOS) were measured (n = 12) by the Griess assay and an enzyme-linked immunosorbent assay, respectively following incubation (24 h) of human-derived U937 monocytes/macrophages with CRP isoforms [(nCRP) = 500 and 1,000 µg/ml; (mCRP) = 100 and 250 µg/ml] in the absence or presence of 17 beta-estradiol (1 × 10−7, 1 × 10−8, and 1 × 10−9 M). The response to each CRP isoform and estrogen was dependent on the differentiation and activation status of cells. Monocytes with or without prior LPS-activation significantly increased (P < 0.01) NO/iNOS production when treated with mCRP. The mCRP isoform had no effect (P > 0.05) on NO/iNOS production by unactivated or LPS-activated macrophages, whereas nCRP significantly (P < 0.05) reduced NO/iNOS production by macrophages, with or without prior LPS-activation. The nCRP isoform had opposing actions on monocytes, significantly (P < 0.01) increasing and reducing NO/iNOS by unactivated and LPS-activated monocytes, respectively. Estrogen significantly (P < 0.01) reversed nCRP-mediated NO inhibition by unactivated macrophages but decreased CRP-induced NO by unactivated monocytes treated with nCRP or mCRP and LPS-activated monocytes treated with mCRP. NO was differentially mediated by CRP isoforms in a cell-type/state-specific manner, with production corresponding to concomitant changes in iNOS levels. Collectively, the findings indicate nCRP and estrogen predominantly reduce NO production, whereas mCRP increases NO production. This supports growing evidence that mCRP exacerbates inflammation while nCRP and estrogen dampen the overall inflammatory response. Therapeutic strategies that restore estrogen levels to those found in youth and promote the stability of nCRP or/and prevent the formation of mCRP may reduce NO production in age-related inflammatory conditions.

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Section: Resultssupporting

confidence: 90%

The Effect of C-Reactive Protein Isoforms on Nitric Oxide Production by U937 Monocytes/Macrophages

et al. 2018

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“…A cell-based experiment partly revealed the mechanism with which EGCG inhibits 3T3-L1 preadipocyte differentiation, activates AMPK, and decreases fat accumulation [ 28 ]. GTCs could also have protective effects on endothelial cells as other antioxidants do, by inhibiting the adhesion of monocytes [ 29 , 30 ]. In another cell-based study, EGCG was shown to suppress the mRNA expression of monocyte chemotactic protein-1, which accelerates the progress of atherosclerosis by promoting the adhesion of monocytes [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Daily Coffee and Green Tea Consumption Is Inversely Associated with Body Mass Index, Body Fat Percentage, and Cardio-Ankle Vascular Index in Middle-Aged Japanese Women: A Cross-Sectional Study

et al. 2020

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This study aimed to investigate the links between coffee (CF)/green tea (GT) consumption and body composition/cardiovascular parameters in middle-aged Japanese women. We conducted a cross-sectional study of 232 Japanese women aged 40–65 years who had been referred to the menopause clinic of Tokyo Medical and Dental University Hospital between November 2007 and August 2017. Body composition, cardiovascular parameters, and CF/GT consumption frequency were evaluated on their initial visits, using a body composition analyzer, vascular screening system, and brief-type self-administered diet history questionnaire, respectively. We investigated the associations between variables using multivariate logistic regression. After adjustment for age, menopausal status, and other factors, daily CF consumption was inversely associated with high body mass index (BMI) (adjusted odds ratio, 0.14; 95% confidence interval, 0.14–0.96) and body fat percentage (BF%) (0.33; 0.14–0.82), and daily GT consumption with high BF% (0.36; 0.14–0.96). Daily CF + GT consumption was also inversely associated with high BMI (0.15; 0.05–0.50) and BF% (0.30; 0.12–0.74). In pre- and perimenopausal women, daily CF + GT consumption was inversely associated with high cardio-ankle vascular index (CAVI) (0.05; 0.003–0.743). In conclusion, daily CF/GT consumption was inversely associated with high BMI, BF%, and CAVI in middle-aged Japanese women.

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“…The endothelium was partially protected from monocytic cell adhesion by pretreatment with L-cysteine ethyl ester (cell-permeable) ( Figure S2 ). Hence, it is possible that G6PD deficiency-induced cellular dysfunctions could be prevented by supplementation with the micronutrient L-cysteine, which directly boosts the levels of the major antioxidant GSH and increases the transcription of G6PD [ 32 , 33 , 34 , 35 ], because G6PD deficiency increases oxidative stress and adversely affects the endothelium by activating TGF-β/Smad/NOX components. Future studies are needed to investigate whether supplementation with L-cysteine can be beneficial to the G6PD-deficient population.…”

Section: Discussionmentioning

confidence: 99%

“…The diluted siRNA was combined with diluted lipofectamine, followed by an additional incubation at room temperature for 30 min to allow siRNA complexes to form before addition to the cells. Cells were incubated with siRNA medium for 4 h at 37 °C, followed by incubation with complete fresh media for the next 24 h. The double-stranded control siRNA-A (Santa Cruz Biotechnology, sc-37007) does not match any other current sequences used as a control in the experiments [ 34 , 35 , 40 ]. After the transfection procedure, G6PD-deficient cells were treated with basal medium at different time points, similar to the treatment protocol described elsewhere in this paper.…”

Section: Methodsmentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase Deficiency Activates Endothelial Cell and Leukocyte Adhesion Mediated via the TGFβ/NADPH Oxidases/ROS Signaling Pathway

Parsanathan

Jain

2020

IJMS

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic inherited trait among humans, affects ~7% of the global population, and is associated with excess risk of cardiovascular disease (CVD). Transforming growth factor-β (TGF-β) regulates immune function, proliferation, epithelial-mesenchymal transition, fibrosis, cancer, and vascular dysfunction. This study examined whether G6PD deficiencies can alter TGF-β-mediated NADPH oxidases (NOX) and cell adhesion molecules (CAM) in human aortic endothelial cells (HAEC). Results show that treatment with high glucose and the saturated free fatty acid palmitate significantly downregulated G6PD; in contrast, mRNA levels of TGF-β components, NOX and its activity, and reactive oxygen species (ROS) were significantly upregulated in HAEC. The expression levels of TGF-β and its receptors, NOX and its activity, and ROS were significantly higher in HG-exposed G6PD-deficient cells (G6PD siRNA) compared to G6PD-normal cells. The protein levels of adhesion molecules (ICAM-1 and VCAM-1) and inflammatory cytokines (MCP-1 and TNF) were significantly increased in HG-exposed G6PD-deficient cells compared to G6PD-normal cells. The adherence of monocytes (SC cells) to HAEC was significantly elevated in HG-treated G6PD-deficient cells compared to control cells. Pharmacological inhibition of G6PD enhances ROS, NOX and its activity, and endothelial monocyte adhesion; these effects were impeded by NOX inhibitors. The inhibition of TGF-β prevents NOX2 and NOX4 mRNA expression and activity, ROS, and adhesion of monocytes to HAEC. L-Cysteine ethyl ester (cell-permeable) suppresses the mRNA levels of TGF-β and its receptors, along with NOX2 and NOX4, and decreases NOX activity, ROS, and adhesion of monocytes to HAEC. This suggests that G6PD deficiency promotes TGF-β/NADPH oxidases/ROS signaling, the expression of ICAM-1 and VCAM-1, and the adhesion of leukocytes to the endothelial monolayer, which can contribute to a higher risk for CVD.

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l-Cysteine in vitro can restore cellular glutathione and inhibits the expression of cell adhesion molecules in G6PD-deficient monocytes

Cited by 31 publications

References 60 publications

The Effect of C-Reactive Protein Isoforms on Nitric Oxide Production by U937 Monocytes/Macrophages

The Effect of C-Reactive Protein Isoforms on Nitric Oxide Production by U937 Monocytes/Macrophages

Daily Coffee and Green Tea Consumption Is Inversely Associated with Body Mass Index, Body Fat Percentage, and Cardio-Ankle Vascular Index in Middle-Aged Japanese Women: A Cross-Sectional Study

Glucose-6-Phosphate Dehydrogenase Deficiency Activates Endothelial Cell and Leukocyte Adhesion Mediated via the TGFβ/NADPH Oxidases/ROS Signaling Pathway

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