Clavulanic acid inhibits MPP+-induced ROS generation and subsequent loss of dopaminergic cells

Gina Chun Kost, Senthil Selvaraj, Young Bok Lee, Deog Joong Kim, Chang Ho Ahn, Brij B. Singh

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Clavulanic acid is a psychoactive compound that has been shown to modulate central nervous system activity. Importantly, in neurotoxin-induced animal models, clavulanic acid has been shown to improve motor function (Huh et al., 2010) suggesting that it can be neuroprotective; however, the mechanism as how clavulanic acid can induce neuroprotection is not known. We demonstrate here that clavulanic acid abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) which mimics Parkinson's disease (PD) by inducing neurodegeneration. To further establish the mechanism we identified that clavulanic acid inhibits neurotoxin-induced loss of mitochondrial membrane potential and ROS production. Consistent with these results, neurotoxin-induced increase in Bax levels was also decreased in clavulanic acid treated cells. Importantly, neurotoxin-induced release of cytochrome c levels as well as caspase activation was also inhibited in clavulanic acid treated cells. In addition, Bcl-xl levels were also restored and the Bcl-xl/Bax ratio that is critical for inducing apoptosis was increased in clavulanic acid treated cells. Overall, these results suggest that clavulanic acid is intimately involved in inhibiting neurotoxin-induced loss of mitochondrial function and induction of apoptosis that contributes towards neuronal survival.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalBrain Research
Volume1469
DOIs
StatePublished - Aug 21 2012
Externally publishedYes

Keywords

  • Apoptosis
  • Clavulanic acid
  • MPTP
  • Mitochondria
  • Neuroprotection
  • Parkinson's disease (PD)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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