Up-regulation of astroglial heme oxygenase-1 by a synthetic (S)-verbenone derivative LMT-335 ameliorates oxygen-glucose deprivation-evoked injury in cortical neurons

Chung Ju, Sumi Song, Minkyoung Kim, Yongseok Choi, Won Ki Kim

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Excessive generation of free radicals is regarded as a major detrimental factor in cerebral ischemic insults. Neurons are particularly vulnerable to oxidative stress due to their limited anti-oxidant capacity. As an important source of antioxidants in the brain, astroglia are now thought to be attractive targets for pharmacological interventions to reduce neuronal oxidative stress in ischemic stroke. In the present study, we synthesized a novel antioxidant, the (1S)-(-)-verbenone derivative LMT-335, and investigated its anti-ischemic activities. In rat cortical neuronal/glial co-cultures, LMT-335 significantly reduced oxygen-glucose deprivation (OGD)/reoxygenation (R)-induced neuronal injury. Although it did not inhibit N-methyl d-aspartate-induced excitotoxicity, LMT-335 significantly reduced OGD/R-evoked intracellular oxidative stress. However, the oxygen radical absorbance capacity assay and 1,1-diphenyl-2-picrylhydrazyl assay showed that the free radical scavenging activities of LMT-335 were lower than those of trolox. Instead, LMT-335 significantly increased the astroglial expression of heme oxygenase-1 (HO-1), a well-known anti-oxidant stress protein, as evidenced by immunocytochemistry and immunoblot analyses. Moreover, a selective HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly blocked the anti-ischemic effect of LMT-335. The present findings indicate that LMT-335 exerts neuroprotective effects against OGD/R by up-regulation of HO-1 in astroglial cells. Our data suggest that astroglial HO-1 represents a potential therapeutic target for the treatment of ischemic stroke.

Original languageEnglish
Pages (from-to)484-489
Number of pages6
JournalBiochemical and biophysical research communications
Issue number3
Publication statusPublished - 2013 Feb 15

Bibliographical note

Funding Information:
This study was supported by a grant (#A100766 to W.-K. Kim) from the Korea Health Technology R&D Project, the Ministry of Health & Welfare and by a grant (#2012K001112 to W.-K. Kim) from Brain Research Center of the 21st Century Frontier Research Program, the Ministry of Science and Technology, Republic of Korea . We are grateful to Dr. Paul L. Prather for his kind and careful reading.


  • Astroglia
  • Cerebral ischemia
  • Heme-oxygenase-1
  • LMT-335
  • Oxidative stress
  • Oxygen-glucose deprivation/re-oxygenation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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