Influence of intracellular zinc on cultures of rat cardiac neural crest cells

Hsunhui Yang, Carl L Keen, Louise Lanoue

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: Developmental zinc (Zn) deficiency increases the incidence of heart anomalies in rat fetuses, in regions and structures derived from the outflow tract. Given that the development of the outflow tract requires the presence of cardiac neural crest cells (cNCC), we speculated that Zn deficiency selectively kills cNCC and could lead to heart malformations. METHODS: Cardiac NCC were isolated from E10.5 rat embryos and cultured in control media (CTRL), media containing 3 μM of the cell permeable metal chelator N, N, N', N'-tetrakis (2-pyridylmethyl) ethylene diamine (TPEN), or in TPEN-treated media supplemented with 3 μM Zn (TPEN + Zn). Cardiac NCC were collected after 6, 8, and 24 h of treatment to assess cell viability, proliferation, and apoptosis. RESULTS: The addition of TPEN to the culture media reduced free intracellular Zn pools and cell viability as assessed by low ATP production, compared to cells grown in control or Zn-supplemented media. There was an accumulation of reactive oxygen species, a release of mitochondrial cytochrome c into the cytoplasm, and an increased cellular expression of active caspase-3 in TPEN-treated cNCC compared to cNCC cultured in CTRL or TPEN + Zn media. CONCLUSION: Zn deficiency can result in oxidative stress in cNCC, and subsequent decreases in their population and metabolic activity. These data support the concept that Zn deficiency associated developmental heart defects may arise in part as a consequence of altered cNCC metabolism.

Original languageEnglish (US)
Pages (from-to)11-22
Number of pages12
JournalBirth Defects Research Part B - Developmental and Reproductive Toxicology
Volume104
Issue number1
DOIs
StatePublished - Feb 1 2015

Fingerprint

Neural Crest
Zinc
Rats
Cell Survival
Cells
Oxidative stress
Diamines
Congenital Heart Defects
Cell proliferation
Chelating Agents
Cytochromes c
Metabolism
Caspase 3
Culture Media
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
Reactive Oxygen Species
Cytoplasm
Oxidative Stress
Fetus
Embryonic Structures

Keywords

  • Apoptosis
  • Neural crest cells
  • Oxidative damage
  • Zinc

ASJC Scopus subject areas

  • Developmental Biology
  • Embryology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Influence of intracellular zinc on cultures of rat cardiac neural crest cells. / Yang, Hsunhui; Keen, Carl L; Lanoue, Louise.

In: Birth Defects Research Part B - Developmental and Reproductive Toxicology, Vol. 104, No. 1, 01.02.2015, p. 11-22.

Research output: Contribution to journalArticle

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