The heme precursor delta-aminolevulinate blocks peripheral myelin formation

Natalia Felitsyn, Colin McLeod, Albert L. Shroads, Peter W. Stacpoole, Lucia Notterpek

Research output: Contribution to journalArticle

Abstract

Delta-aminolevulinic acid (δ-ALA) is a heme precursor implicated in neurological complications associated with porphyria and tyrosinemia type I. Delta-ALA is also elevated in the urine of animals and patients treated with the investigational drug dichloroacetate (DCA). We postulated that δ-ALA may be responsible, in part, for the peripheral neuropathy observed in subjects receiving DCA. To test this hypothesis, myelinating cocultures of Schwann cells and sensory neurons were exposed to δ-ALA (0.1-1 mM) and analyzed for the expression of neural proteins and lipids and markers of oxidative stress. Exposure of myelinating samples to δ-ALA is associated with a pronounced reduction in the levels of myelin-associated lipids and proteins, including myelin protein zero and peripheral myelin protein 22. We also observed an increase in protein carbonylation and the formation of hydroxynonenal and malondialdehyde after treatment with δ-ALA. Studies of isolated Schwann cells and neurons indicate that glial cells are more vulnerable to this pro-oxidant than neurons, based on a selective decrease in the expression of mitochondrial respiratory chain proteins in glial, but not in neuronal, cells. These results suggest that the neuropathic effects of δ-ALA are attributable, at least in part, to its pro-oxidant properties which damage myelinating Schwann cells.

Original languageEnglish (US)
Pages (from-to)2068-2079
Number of pages12
JournalJournal of Neurochemistry
Volume106
Issue number5
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Fingerprint

Schwann Cells
Myelin Sheath
Heme
Neurons
Neuroglia
Reactive Oxygen Species
Cells
Myelin P0 Protein
Tyrosinemias
Protein Carbonylation
Investigational Drugs
Myelin Proteins
Lipids
Porphyrias
Aminolevulinic Acid
Proteins
Peripheral Nervous System Diseases
Sensory Receptor Cells
Electron Transport
Coculture Techniques

Keywords

  • Delta-aminolevulinate
  • Demyelination
  • Dichloroacetate
  • Oxidative stress
  • Peripheral neuropathy
  • Schwann cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Felitsyn, N., McLeod, C., Shroads, A. L., Stacpoole, P. W., & Notterpek, L. (2008). The heme precursor delta-aminolevulinate blocks peripheral myelin formation. Journal of Neurochemistry, 106(5), 2068-2079. https://doi.org/10.1111/j.1471-4159.2008.05552.x

The heme precursor delta-aminolevulinate blocks peripheral myelin formation. / Felitsyn, Natalia; McLeod, Colin; Shroads, Albert L.; Stacpoole, Peter W.; Notterpek, Lucia.

In: Journal of Neurochemistry, Vol. 106, No. 5, 01.09.2008, p. 2068-2079.

Research output: Contribution to journalArticle

Felitsyn, N, McLeod, C, Shroads, AL, Stacpoole, PW & Notterpek, L 2008, 'The heme precursor delta-aminolevulinate blocks peripheral myelin formation', Journal of Neurochemistry, vol. 106, no. 5, pp. 2068-2079. https://doi.org/10.1111/j.1471-4159.2008.05552.x
Felitsyn, Natalia ; McLeod, Colin ; Shroads, Albert L. ; Stacpoole, Peter W. ; Notterpek, Lucia. / The heme precursor delta-aminolevulinate blocks peripheral myelin formation. In: Journal of Neurochemistry. 2008 ; Vol. 106, No. 5. pp. 2068-2079.
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