ArticleOxidative medicine and cellular longevity2016
Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal.
Article in Oxidative medicine and cellular longevity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- A Systematic Review of the Various Effect of Arsenic on Glutathione Synthesis In Vitro and In Vivo.BioMed research international · 2020Pooled it
- Sulfur-Containing Amino Acid Homeostasis in the Central Nervous System: From Physiology Regulation to Metal-Induced Neurotoxicity.Metabolites · 2026Review
- Article
- Detection and characterisation of novel alternative splicing variants of the mitochondrial folate enzyme MTHFD2.Molecular biology reports · 2020Article
- Andrographolide attenuates bupivacaine-induced cytotoxicity in SH-SY5Y cells through preserving Akt/mTOR activity.Drug design, development and therapy · 2019Article
- Vitamin B12 protects against DNA damage induced by hydrochlorothiazide.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2018Article
- Prevalence and risk factors of hypertension in acclimatized lowlanders staying at high altitude for different durations.Journal of human hypertension · 2018Article
- Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System.Antioxidants & redox signaling · 2017Review
- Impaired cross-talk between the thioredoxin and glutathione systems is related to ASK-1 mediated apoptosis in neuronal cells exposed to mercury.Redox biology · 2017Article
- Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells.Neural regeneration research · 2016Article
Corrections and comments
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Authors and funding
7 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The folate and cobalamin (Cbl-) dependent enzyme methionine synthase (MS) is highly sensitive to oxidation and its activity affects all methylation reactions. Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts. Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes. MS activity was dependent upon methylcobalamin (MeCbl) or the combination of hydroxocobalamin (OHCbl) and S-adenosylmethionine (SAM). OHCbl-based activity was eliminated by depletion of the antioxidant glutathione (GSH) but could be rescued by provision of either glutathionylcobalamin (GSCbl) or MeCbl. Pretreatment of cells with lead, arsenic, aluminum, mercury, or the ethylmercury-containing preservative thimerosal lowered GSH levels and inhibited MS activity in association with decreased uptake of cysteine, which is rate-limiting for GSH synthesis. Thimerosal treatment decreased cellular levels of GSCbl and MeCbl. These findings indicate that the alternatively spliced form of MS expressed in SH-SY5Y human neuronal cells is sensitive to inhibition by thimerosal and neurotoxic metals, and lower GSH levels contribute to their inhibitory action.
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