Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to paraquat

Mitochondrial dysfunction and oxidative stress

Fang Wang, Rodrigo Franco-Cruz, Maciej Skotak, Gang Hu, Namas Chandra

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Recent studies suggest that traumatic brain injury (TBI) and pesticide exposure increase the risk of Parkinson's disease (PD), but the molecular mechanisms involved remain unclear. Using an in vitro model of TBI, we evaluated the role of mitochondrial membrane potential (δΨm) and mitochondrial reactive oxygen species (ROS) induced by stretch on dopaminergic cell death upon paraquat exposure. Human dopaminergic neuroblastoma SH-SY5Y cells grown on silicone membrane were stretched at mild (25%) and moderate (50%) strain prior to paraquat exposure. We observed that moderate stretch (50% strain) increased the vulnerability of cells to paraquat demonstrated by the loss of plasma membrane integrity (propidium iodide-uptake) and decreased mitochondrial activity (MTT assay). Mitochondrial depolarization occurred immediately after stretch, while mitochondrial ROS increased rapidly and remained elevated for up to 4. h after the stretch injury. Intracellular glutathione (GSH) stores were also transiently decreased immediately after moderate stretch. Cells treated with paraquat, or moderate stretch exhibited negligible mitochondrial depolarization at 48. h post treatment, whereas in cells stretched prior to paraquat exposure, a significant mitochondrial depolarization occurred compared to samples exposed to either paraquat or stretch. Moderate stretch also increased mitochondrial ROS formation, as well as exacerbated intracellular GSH loss induced by paraquat. Overexpression of manganese superoxide dismutase (MnSOD) markedly diminished the deleterious effects of stretch in paraquat neurotoxicity. Our findings demonstrate that oxidative stress induced by mitochondrial dysfunction plays a critical role in the synergistic toxic effects of stretch (TBI) and pesticide exposure. Mitigation of oxidative stress via mitochondria-targeted antioxidants appears an attractive route for treatment of neurodegeneration mediated by TBI.

Original languageEnglish (US)
Pages (from-to)54-63
Number of pages10
JournalNeuroToxicology
Volume41
DOIs
StatePublished - Mar 1 2014

Fingerprint

Paraquat
Oxidative stress
Cell death
Oxidative Stress
Cell Death
Brain
Depolarization
Reactive Oxygen Species
Pesticides
Membranes
Mitochondria
Propidium
Mitochondrial Membrane Potential
Poisons
Silicones
Cell membranes
Neuroblastoma
Superoxide Dismutase
Glutathione
Parkinson Disease

Keywords

  • Mitochondria
  • MnSOD
  • Paraquat
  • Reactive oxygen species
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to paraquat : Mitochondrial dysfunction and oxidative stress. / Wang, Fang; Franco-Cruz, Rodrigo; Skotak, Maciej; Hu, Gang; Chandra, Namas.

In: NeuroToxicology, Vol. 41, 01.03.2014, p. 54-63.

Research output: Contribution to journalArticle

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