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Vitamin C controls neuronal necroptosis under oxidative stress

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Abstract
Under physiological conditions, vitamin C is the main antioxidant found in the central nervous system and is found in two states: reduced as ascorbic acid (AA) and oxidized as dehydroascorbic acid (DHA). However, under pathophysiological conditions, AA is oxidized to DHA. The oxidation of AA and subsequent production of DHA in neurons are associated with a decrease in GSH concentrations, alterations in glucose metabolism and neuronal death. To date, the endogenous molecules that act as intrinsic regulators of neuronal necroptosis under conditions of oxidative stress are unknown. Here, we show that treatment with AA regulates the expression of pro- and antiapoptotic genes. Vitamin C also regulates the expression of RIPK1/MLKL, whereas the oxidation of AA in neurons induces morphological alterations consistent with necroptosis and MLKL activation. The activation of necroptosis by AA oxidation in neurons results in bubble formation, loss of membrane integrity, and ultimately, cellular explosion. These data suggest that necroptosis is a target for cell death induced by vitamin C.
Keywords
CELL-DEATH, DEHYDROASCORBIC ACID, CANCER-CELLS, NECROSTATIN-1, PROTECTION, INDUCED APOPTOSIS, HYPOXIA, MLKL, ACTIVATION, NECROSIS, ISCHEMIA, Vitamin C, Ascorbic acid, Dehydroascorbic acid, Necroptosis, Neuronal, death, Live cell microscopy

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Citation

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MLA
Ferrada, Luciano, et al. “Vitamin C Controls Neuronal Necroptosis under Oxidative Stress.” REDOX BIOLOGY, vol. 29, 2020.
APA
Ferrada, L., Barahona, M. J., Salazar, K., Vandenabeele, P., & Nualart, F. (2020). Vitamin C controls neuronal necroptosis under oxidative stress. REDOX BIOLOGY, 29.
Chicago author-date
Ferrada, Luciano, Maria Jose Barahona, Katterine Salazar, Peter Vandenabeele, and Francisco Nualart. 2020. “Vitamin C Controls Neuronal Necroptosis under Oxidative Stress.” REDOX BIOLOGY 29.
Chicago author-date (all authors)
Ferrada, Luciano, Maria Jose Barahona, Katterine Salazar, Peter Vandenabeele, and Francisco Nualart. 2020. “Vitamin C Controls Neuronal Necroptosis under Oxidative Stress.” REDOX BIOLOGY 29.
Vancouver
1.
Ferrada L, Barahona MJ, Salazar K, Vandenabeele P, Nualart F. Vitamin C controls neuronal necroptosis under oxidative stress. REDOX BIOLOGY. 2020;29.
IEEE
[1]
L. Ferrada, M. J. Barahona, K. Salazar, P. Vandenabeele, and F. Nualart, “Vitamin C controls neuronal necroptosis under oxidative stress,” REDOX BIOLOGY, vol. 29, 2020.
@article{8647319,
  abstract     = {Under physiological conditions, vitamin C is the main antioxidant found in the central nervous system and is found in two states: reduced as ascorbic acid (AA) and oxidized as dehydroascorbic acid (DHA). However, under pathophysiological conditions, AA is oxidized to DHA. The oxidation of AA and subsequent production of DHA in neurons are associated with a decrease in GSH concentrations, alterations in glucose metabolism and neuronal death. To date, the endogenous molecules that act as intrinsic regulators of neuronal necroptosis under conditions of oxidative stress are unknown. Here, we show that treatment with AA regulates the expression of pro- and antiapoptotic genes. Vitamin C also regulates the expression of RIPK1/MLKL, whereas the oxidation of AA in neurons induces morphological alterations consistent with necroptosis and MLKL activation. The activation of necroptosis by AA oxidation in neurons results in bubble formation, loss of membrane integrity, and ultimately, cellular explosion. These data suggest that necroptosis is a target for cell death induced by vitamin C.},
  articleno    = {101408},
  author       = {Ferrada, Luciano and Barahona, Maria Jose and Salazar, Katterine and Vandenabeele, Peter and Nualart, Francisco},
  issn         = {2213-2317},
  journal      = {REDOX BIOLOGY},
  keywords     = {CELL-DEATH,DEHYDROASCORBIC ACID,CANCER-CELLS,NECROSTATIN-1,PROTECTION,INDUCED APOPTOSIS,HYPOXIA,MLKL,ACTIVATION,NECROSIS,ISCHEMIA,Vitamin C,Ascorbic acid,Dehydroascorbic acid,Necroptosis,Neuronal,death,Live cell microscopy},
  language     = {eng},
  pages        = {12},
  title        = {Vitamin C controls neuronal necroptosis under oxidative stress},
  url          = {http://dx.doi.org/10.1016/j.redox.2019.101408},
  volume       = {29},
  year         = {2020},
}

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