ArticleBiochemical and biophysical research communications2012
Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells.
Article in Biochemical and biophysical research communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
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- The Role of GCH1 Deficiency and Tetrahydrobiopterin in Mental Health.International journal of molecular sciences · 2025Article
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- Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress.Frontiers in pharmacology · 2023Article
- Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid.Antioxidants (Basel, Switzerland) · 2022Review
- The Influence of Dietary Supplementations on Neuropathic Pain.Life (Basel, Switzerland) · 2022Review
- Apex Predator Nematodes and Meso-Predator Bacteria Consume Their Basal Insect Prey through Discrete Stages of Chemical Transformations.mSystems · 2022Article
- Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back.Molecules (Basel, Switzerland) · 2022Review
- 3-Polymers · 2022Article
- Antidepressant Like Effect of Ascorbic Acid in Mice: Possible Involvement of NO-sGC-cGMP Signaling.Neurochemical research · 2022Article
- Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients.Critical care (London, England) · 2022Article
- Chemical Stability of Ascorbic Acid Integrated into Commercial Products: A Review on Bioactivity and Delivery Technology.Antioxidants (Basel, Switzerland) · 2022Review
- A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis.Materials today. Bio · 2022Article
- The protective role of vitamin C in the management of COVID-19: A Review.The Journal of the Egyptian Public Health Association · 2021Review
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ascorbic acid is well known to acutely stimulate norepinephrine synthesis in neurosecretory cells, but it has also been shown over several days to increase tyrosine hydroxylase mRNA and norepinephrine synthesis in cultured neurons. Since tyrosine hydroxylase is the rate-limiting step in catecholamine synthesis, an effect of ascorbate to increase tyrosine hydroxylase protein could contribute to its ability to increase or sustain catecholamine synthesis. Therefore, we evaluated whether tyrosine hydroxylase protein expression and function is increased in SH-SY5Y neuroblastoma cells by physiologically relevant intracellular ascorbate concentrations. SH-SY5Y neuroblastoma cells did not contain ascorbate and had only very low levels of norepinephrine in culture with L-tyrosine, the substrate for tyrosine hydroxylase. However, treatment of cells with ascorbate for 6 h or more markedly increased norepinephrine synthesis, such that intracellular ascorbate and norepinephrine increased in parallel with half maximal intracellular concentrations of about 1 mM ascorbate and 150 μM norepinephrine. This increase was enhanced by supplementing tetrahydrobiopterin, but was not mimicked by several antioxidants or by catalase or superoxide dismutase. Tyrosine hydroxylase protein expression increased at intracellular ascorbate concentrations above 1.5 mM. This contributed to norepinephrine generation, which was decreased 50-60% by inhibition of protein synthesis with cycloheximide at high intracellular ascorbate. These results suggest that expected physiologic neuronal ascorbate concentrations enhance norepinephrine synthesis both by maintaining tetrahydrobiopterin and increasing tyrosine hydroxylase expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.