Inhibition of Glutathione Synthesis Induced by Exhaustive Running Exercise via the Decreased Influx Rate of L-Cysteine in Rat Erythrocytes

Xiong, Yanlei; Zhou, Shuai; Yu, Zhenhai; Wang, Zhiqiang; Li, Yuling; Yan, Jingtong; Cai, Yu Jun; Zhang, Wenqian

doi:10.1159/000453193

Cited by 15 publications

(12 citation statements)

References 47 publications

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“…The activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in CD4 + T cells were measured by colorimetric analysis [ 20 ]. GSH-Px activity was detected using the DTNB method [ 21 ], CAT activity was measured using the ammonium molybdate method [ 22 ], and SOD activity was measured using the xanthine-oxidase method [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

hPMSCs protects against d-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

et al. 2020

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Background Mesenchymal stem cells (MSCs) were considered a regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a d-gal-induced mouse aging model. Methods In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, d-gal group, hPMSC group, and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were co-cultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging-related proteins was detected by Western blotting, RT-PCR, and confocal microscopy. Results We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal-positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression, and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC, and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells. Conclusions Our results indicate that hPMSCs attenuate d-gal-induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.

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Section: Methodsmentioning

confidence: 99%

hPMSCs protects against d-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

et al. 2020

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“…Glutathione (GSH) is an important redox active biomolecule critical in maintaining cellular and organism homeostasis [4,5]. Previous studies suggested that abnormal metabolism of GSH was closely related with various pathological and physiological conditions [6,7]. Whillier et al showed that the glutathione synthesis rate significantly decreased in stored RBCs after 6 weeks [8].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Glutathione Synthesis via Decreased Glucose Metabolism in Stored RBCs

Xiong

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although red blood cells (RBCs) transfusions can be lifesaving, they are not without risk. RBCs storage is associated with the abnormal metabolism of glutathione (GSH), which may increase the risk of the oxidative damage of RBCs after transfusion. The responsible mechanisms remain unknown. Methods: We determined the L-cysteine efflux and influx by evaluating the changes of free -SH concentrations in stored RBCs. The glutamate cysteine ligase (GCL) activities and protein content in stored RBCs was determined by fluorescence assay and western blotting. In addition, the glucose metabolism enzyme activity of RBCs was measured by spectrophotometric assay under in vitro incubation conditions. Results: We found that both L-cysteine transport and GCL activity significantly declined, thereby inducing the dysfunction of GSH synthesis during blood storage, which could be attenuated by ATP supplement and DTT treatment. In addition, the glycometabolic enzyme (G6PDH, HK, PK and LDH) activity significantly decreased after 6 weeks storage. Oxidant stress-induced dysfunction in glucose metabolism was the driving force for decreased GSH synthesis during storage. Conclusion: These experimental findings reflect an underlying molecular mechanism that oxidant stress induced glucose metabolism dysfunction contribute to decreased GSH synthesis in stored RBCs.

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“…Similar oxidative effects of extreme exercise that induce RBC membrane lipid oxidation were also reported. 32 In exhausted animals, the free radicals produced from the ATP-generating system (which include O2 •− and H2O2, respectively) enhanced exercise-related oxidative stress. 33 These free radicals which are dismasted by SOD, an antioxidant defense against hydrogen peroxide could be finally wear off by glutathione peroxidase.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Effect of Vitamin C on Myocardial Angiogenesis Under Oxidative Stress Induced by Exhaustive Exercise in Rat

et al. 2018

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Background: The main purpose of the present study was to assess the effects of exhaustive swimming with the consumption of a vitamin C supplement on indices of myocardial oxidative stress and gene expression related to angiogenesis. Methods: Wistar rats were randomly divided into six groups of normal (C), 100 and 200 mg/kg of vitamin C, (VC100 and VC200), exercise with 100 and 200 mg/kg of vitamin C (Ex+VC100 and Ex+VC200) and exercise without treatment (Ex). Finally, the serum activity of serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) and heart tissue oxidant/antioxidant parameters, besides gene expression of Vascular endothelial growth factor-B (VEGF-B), angiopoietin 1 (ANGPT-1) and matrix metalloproteinases 2 (MMP-2) was measured. Results: Significant increase in LDH level was seen in group Ex which was remarkably attenuated in group Ex+VC200 (p<0.001). The tissue oxidative stress was observed in group Ex where daily intake of vitamin C could remarkably regulate this property (p<0.01). Vitamin C could ameliorate significant upper gene expression of VEGF-B and MMP-2 remarkably (p<0.05). Conclusion: Oxidative condition in myocardial besides over expression of MMP-2, could be concluded as a detrimental condition resulting from exhaustive swimming that continued by the proteolytic release of CK and LDH from the muscle. Upper gene expression of VEGF-B and MMP-2 besides no changes of ANGPT-1 can be concluded as an early stage of angiogenesis. All these events were somehow attenuated by vitamin C which confirmed its beneficial effects as an antioxidant and the role of oxidation properties in the regulation of angiogenesis.

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Inhibition of Glutathione Synthesis Induced by Exhaustive Running Exercise via the Decreased Influx Rate of L-Cysteine in Rat Erythrocytes

Cited by 15 publications

References 47 publications

hPMSCs protects against d-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

hPMSCs protects against d-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

Inhibition of Glutathione Synthesis via Decreased Glucose Metabolism in Stored RBCs

Evaluating the Effect of Vitamin C on Myocardial Angiogenesis Under Oxidative Stress Induced by Exhaustive Exercise in Rat

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