Protective Effect of Borneolum on ER Stress-induced Damage in C6 Glial Cells

ER Stress에 의해 유발된 C6 Glial Cells의 손상에 대한 용뇌(龍腦)의 보호효과

  • Jeon, In-Cheol (Department of Oriental Internal Medicine, School of Oriental Medicine, Wonkwang University) ;
  • Bang, Chang-Ho (Department of Oriental Internal Medicine, School of Oriental Medicine, Wonkwang University) ;
  • Moon, Byung-Soon (Department of Oriental Internal Medicine, School of Oriental Medicine, Wonkwang University) ;
  • Lee, In (Department of Oriental Internal Medicine, School of Oriental Medicine, Wonkwang University)
  • 전인철 (원광대학교 한의과대학 한방내과학교실) ;
  • 방창호 (원광대학교 한의과대학 한방내과학교실) ;
  • 문병순 (원광대학교 한의과대학 한방내과학교실) ;
  • 이인 (원광대학교 한의과대학 한방내과학교실)
  • Published : 2009.12.25

Abstract

Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER response is characterized by changes in specific proteins, induction of ER chaperones and degradation of misfolded proteins. Also, the pathogenesis of several diseases like Alzheimer's disease, neuronal degenerative diseases, and diabetes reveal the role of ER stress as one of the causative mechanisms. Borneolum has been used for neuronal disease in oriental medicine. In the present study, the protective effect of borneolum on thapsigargin-induced apoptosis in rat C6 glial cells. Treatment with C6 glial cells with 5 uM thapsigargin caused the loss of cell viability, and morphological change, which was associated with the elevation of intracellular $Ca^{++}$ level, the increase in Grp78 and CHOP and cleavage of pro-caspase 12 Furthermore, thapsigargin induced Grp98, XBP1, and ATF4 protein expression in C6 glial cells. Borneolum reduced thapsigargin-induced apoptosis through ER pathways. In the ER pathway, borneolum attenuated thapsigargin-induced elevations in Grp78, CHOP, ATF4, and XBP1 as well as reductions in pro-caspase 12 levels. Also, our data showed that borneolum protected thapsigargin-induced cytotoxicity in astrocytes from rat (P3) brain. Taken together, our data suggest that borneolum is neuroprotective against thapsigargin-induced ER stress in C6 glial cells and astrocytes. Accordingly, borneolum may be therapeutically useful for the treatment of thapsigargin-induced apoptosis in central nervous system.

Keywords

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