A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain

Gerardo Mackenzie, Gabriela A. Salvador, Carolina Romero, Carl L Keen, Patricia I. Oteiza

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Zinc (Zn) deficiency during early development can result in multiple brain abnormalities and altered neuronal functions. In rats, a gestational deficit of Zn can affect the fetal brain cytoskeleton and signaling cascades involved in cellular processes that are central to brain development. In this paper, we tested the hypothesis that oxidative stress is involved in Zn deficiency-induced altered tubulin dynamics and the associated dysregulation of transcription factor NF-κB. For this purpose, we used two cell culture models (rat cortical neurons, human IMR-32 neuroblastoma cells) and an animal model of Zn deficiency. A low rate of in vitro tubulin polymerization, an increase in tubulin oligomers, and a higher protein cysteine oxidation were observed in the Zn-deficient neuronal cells and in gestation day 19 fetal brains obtained from dams fed marginal-Zn diets throughout pregnancy. These alterations could be prevented by treating the Zn-deficient cells with the reducing agent tris(2-carboxyethyl)phosphine or by the presence of N-acetylcysteine (NAC) and α-lipoic acid (LA). Consistent with the above, Zn deficiency-induced tubulin-mediated alterations in transcription factor NF-κB nuclear translocation were prevented by treating IMR-32 cells with LA and NAC. Binding of the NF-κB protein p50, dynein, and karyopherin α (components of the NF-κB transport complex) to β-tubulin as well as the expression of NF-κB-dependent genes (Bcl-2, cyclin D1, and c-myc) was also restored by the addition of LA and NAC to Zn-deficient cells. In conclusion, a deficit in Zn viability could affect early brain development through: (1) an induction of oxidative stress, (2) tubulin oxidation, (3) altered tubulin dynamics, and (4) deregulation of signals (e.g., NF-κB) involved in critical developmental events.

Original languageEnglish (US)
Pages (from-to)480-489
Number of pages10
JournalFree Radical Biology and Medicine
Volume51
Issue number2
DOIs
StatePublished - Jul 15 2011

Fingerprint

Tubulin
Sulfhydryl Compounds
Neurons
Oxidation-Reduction
Zinc
Rats
Brain
Availability
Acetylcysteine
Thioctic Acid
Oxidative stress
Oxidative Stress
Transcription Factors
Karyopherins
Multiple Abnormalities
bcl-2 Genes
Dyneins
Pregnancy
Oxidation
Cyclin D1

Keywords

  • Brain
  • Free radicals
  • NF-κB
  • Redox state
  • Tubulin
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain. / Mackenzie, Gerardo; Salvador, Gabriela A.; Romero, Carolina; Keen, Carl L; Oteiza, Patricia I.

In: Free Radical Biology and Medicine, Vol. 51, No. 2, 15.07.2011, p. 480-489.

Research output: Contribution to journalArticle

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