Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells

M. F. Lombardo, M. R. Ciriolo, G. Rotilio, L. Rossi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.

Original languageEnglish
Pages (from-to)1733-1743
Number of pages11
JournalCellular and Molecular Life Sciences
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

Fingerprint

Neuroblastoma
Copper
Antioxidants
Apoptosis
tetramethylenedisulfotetramine
Chemical activation
Cells
Copper Sulfate
Serial Passage
Oxidative stress
Caspase 9
Caspase 8
Electron Transport Complex IV
Enzymes
Chelating Agents
Starvation
Caspase 3
Superoxide Dismutase
Cultured Cells
Monolayers

Keywords

  • Antioxidant
  • Apoptosis
  • Copper depletion
  • Mitochondria
  • Neuroblastoma
  • Neurodegeneration
  • Oxidativestress

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells. / Lombardo, M. F.; Ciriolo, M. R.; Rotilio, G.; Rossi, L.

In: Cellular and Molecular Life Sciences, Vol. 60, No. 8, 01.08.2003, p. 1733-1743.

Research output: Contribution to journalArticle

@article{175725cbdbd34e078fcda95b96588ab1,
title = "Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells",
abstract = "SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.",
keywords = "Antioxidant, Apoptosis, Copper depletion, Mitochondria, Neuroblastoma, Neurodegeneration, Oxidativestress",
author = "Lombardo, {M. F.} and Ciriolo, {M. R.} and G. Rotilio and L. Rossi",
year = "2003",
month = "8",
day = "1",
doi = "10.1007/s00018-003-3153-1",
language = "English",
volume = "60",
pages = "1733--1743",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "8",

}

TY - JOUR

T1 - Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells

AU - Lombardo, M. F.

AU - Ciriolo, M. R.

AU - Rotilio, G.

AU - Rossi, L.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.

AB - SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.

KW - Antioxidant

KW - Apoptosis

KW - Copper depletion

KW - Mitochondria

KW - Neuroblastoma

KW - Neurodegeneration

KW - Oxidativestress

UR - http://www.scopus.com/inward/record.url?scp=0042830827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042830827&partnerID=8YFLogxK

U2 - 10.1007/s00018-003-3153-1

DO - 10.1007/s00018-003-3153-1

M3 - Article

VL - 60

SP - 1733

EP - 1743

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 8

ER -