ArticleCell death and differentiation2013
Functional significance of glutamate-cysteine ligase modifier for erythrocyte survival in vitro and in vivo.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin.Journal of cellular and molecular medicine · 2016Trial
- Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis.Diabetologia · 2026Article
- Human platelet lysate: a potential therapeutic for intracerebral hemorrhage.Frontiers in neuroscience · 2024Review
- Proteomics analysis reveals differential acclimation of coastal and oceanicFrontiers in microbiology · 2024Article
- Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 SignalingMolecules (Basel, Switzerland) · 2022Article
- Can the administration of platelet lysates to the brain help treat neurological disorders?Cellular and molecular life sciences : CMLS · 2022Review
- Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment.International journal of molecular sciences · 2022Article
- Identification of a Novel Ferroptosis-Related Gene Signature for Prediction of Prognosis in Bladder Urothelial Carcinoma.Bladder cancer (Amsterdam, Netherlands) · 2022Article
- Siegesbeckiae Herba Extract and Chlorogenic Acid Ameliorate the Death of HaCaT Keratinocytes Exposed to Airborne Particulate Matter by Mitigating Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Experimental Babesia rossi infection induces hemolytic, metabolic, and viral response pathways in the canine host.BMC genomics · 2021Article
- Ion Transport in Eryptosis, the Suicidal Death of Erythrocytes.Frontiers in cell and developmental biology · 2020Review
- Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2.Scientific reports · 2016Article
- Oxidative stress in β-thalassaemia and sickle cell disease.Redox biology · 2015Review
- Park7 interacts with p47(phox) to direct NADPH oxidase-dependent ROS production and protect against sepsis.Cell research · 2015Article
- Triggers, inhibitors, mechanisms, and significance of eryptosis: the suicidal erythrocyte death.BioMed research international · 2015Review
- Anti-oxidative stress response genes: bioinformatic analysis of their expression and relevance in multiple cancers.Oncotarget · 2013Article
- Fluoxetine induced suicidal erythrocyte death.Toxins · 2013Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythrocytes endure constant exposure to oxidative stress. The major oxidative stress scavenger in erythrocytes is glutathione. The rate-limiting enzyme for glutathione synthesis is glutamate-cysteine ligase, which consists of a catalytic subunit (GCLC) and a modifier subunit (GCLM). Here, we examined erythrocyte survival in GCLM-deficient (gclm(-/-)) mice. Erythrocytes from gclm(-/-) mice showed greatly reduced intracellular glutathione. Prolonged incubation resulted in complete lysis of gclm(-/-) erythrocytes, which could be reversed by exogenous delivery of the antioxidant Trolox. To test the importance of GCLM in vivo, mice were treated with phenylhydrazine (PHZ; 0.07 mg/g b.w.) to induce oxidative stress. Gclm(-/-) mice showed dramatically increased hemolysis compared with gclm(+/+) controls. In addition, PHZ-treated gclm(-/-) mice displayed markedly larger accumulations of injured erythrocytes in the spleen than gclm(+/+) mice within 24 h of treatment. Iron staining indicated precipitations of the erythrocyte-derived pigment hemosiderin in kidney tubules of gclm(-/-) mice and none in gclm(+/+) controls. In fact, 24 h after treatment, kidney function began to diminish in gclm(-/-) mice as evident from increased serum creatinine and urea. Consequently, while all PHZ-treated gclm(+/+) mice survived, 90% of PHZ-treated gclm(-/-) mice died within 5 days of treatment. In vitro, upon incubation in the absence or presence of additional oxidative stress, gclm(-/-) erythrocytes exposed significantly more phosphatidylserine, a cell death marker, than gclm(+/+) erythrocytes, an effect at least partially due to increased cytosolic Ca(2+) concentration. Under resting conditions, gclm(-/-) mice exhibited reticulocytosis, indicating that the enhanced erythrocyte death was offset by accelerated erythrocyte generation. GCLM is thus indispensable for erythrocyte survival, in vitro and in vivo, during oxidative stress.
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