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Orexin-A protects SH-SY5Y cells against H2O2-induced oxidative damage via the PI3K/MEK1/2/ERK1/2 signaling pathway

Chun-Mei Wang1, Chun-Qing Yang1, Bao-Hua Cheng1

  • 11 Neurobiology Key Laboratory of Jining Medical University in Colleges of Shandong, Jining, P.R. China.

International Journal of Immunopathology and Pharmacology
|July 10, 2018
PubMed

Insights

Orexin-A protects human neuroblastoma cells from oxidative damage by activating the PI3K/MEK/ERK pathway. This finding offers potential therapeutic strategies for neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Orexin-A has known effects on tumor cells.
  • Its neuroprotective role in SH-SY5Y human neuroblastoma cells is unexplored.
  • Oxidative stress from hydrogen peroxide (H2O2) is a significant factor in neurodegeneration.

Purpose of the Study:

  • To investigate the neuroprotective effect of Orexin-A against H2O2-induced oxidative damage in SH-SY5Y cells.
  • To elucidate the underlying molecular mechanisms, focusing on signaling pathways.

Main Methods:

  • SH-SY5Y cells were exposed to H2O2 to induce oxidative damage.
  • Orexin-A pre-treatment was administered to assess its protective effects.
  • Cell viability, apoptosis, and enzyme activity (superoxide dismutase) were measured.
  • Key signaling molecules (MEK1/2, ERK1/2) and pathways (PI3K) were analyzed using inhibitors (LY294002).

Main Results:

  • H2O2 significantly reduced cell viability, increased apoptosis, and decreased superoxide dismutase activity.
  • Orexin-A pre-treatment attenuated these H2O2-induced detrimental effects.
  • Orexin-A inhibited the phosphorylation of MEK1/2 and ERK1/2.
  • The protective effects of Orexin-A were dependent on the PI3K pathway, as evidenced by LY294002 treatment.

Conclusions:

  • Orexin-A exhibits significant neuroprotective effects against H2O2-induced oxidative stress in SH-SY5Y cells.
  • The PI3K/MEK1/2/ERK1/2 signaling pathway is crucial for mediating Orexin-A's neuroprotective actions.
  • These findings suggest Orexin-A as a potential therapeutic agent for nervous system diseases involving oxidative damage.
Keywords:
Orexin-API3K/MEK/ERK pathwayneuroprotective effectoxidative damage

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