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Rotenone-induced death of RGC-5 cells is caspase independent, involves the JNK and p38 pathways and is attenuated by

T A Kamalden1, D Ji, N N Osborne

  • 1Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Level 6, West Wing, Headley Way, Oxford, OX3 9DU, UK.

Neurochemical Research
|February 22, 2012
PubMed

Insights

Rotenone induces cell death in RGC-5 cells via reactive oxygen species and mitogen-activated kinases, not apoptosis or necroptosis. Epigallocatechin gallate (EGCG) and epicatechin (EC) show neuroprotective effects against rotenone toxicity.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mitochondrial complex I inhibition by rotenone is a model for neurodegenerative diseases.
  • RGC-5 cells, a transformed neuronal cell line, are used to study rotenone-induced cell death.
  • Flavonoids are investigated for their potential neuroprotective properties.

Purpose of the Study:

  • To characterize rotenone-induced cell death mechanisms in RGC-5 cells.
  • To evaluate the neuroprotective effects of genistein, EGCG, EC, and baicalin against rotenone toxicity.

Main Methods:

  • RGC-5 cells were treated with rotenone to induce cell death.
  • Cell death markers including reactive oxygen species, DNA breakdown, and phosphatidylserine translocation were assessed.
  • Involvement of specific signaling pathways (JNK, caspases, necroptosis) and kinases (MAPK) was investigated.
  • Neuroprotective effects of flavonoids were evaluated by measuring cell viability and lipid peroxidation.

Main Results:

  • Rotenone induced reactive oxygen species generation, DNA breakdown, and phosphatidylserine translocation in RGC-5 cells.
  • Cell death was JNK-dependent and involved mitogen-activated kinases (p-c-Jun, pJNK, pp38) but not necroptosis or caspase-dependent apoptosis.
  • EGCG and EC significantly reduced rotenone toxicity at 50 μM.
  • Genistein and baicalin showed no significant protective effect against rotenone toxicity.
  • EGCG and EC were more potent than genistein in inhibiting lipid peroxidation.

Conclusions:

  • Rotenone toxicity in RGC-5 cells is mediated by JNK and MAPK pathways, independent of apoptosis and necroptosis.
  • EGCG and EC demonstrate significant neuroprotective potential against rotenone-induced cell death.
  • Flavonoids like EGCG and EC may offer therapeutic benefits in conditions involving mitochondrial dysfunction and oxidative stress.

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