A Carbazole Derivative Protects Cells Against Endoplasmic Reticulum (ER) Stress and Glutathione Depletion

• Miura Hikari

  Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Japan CREST, JST (Japan Science and Technology), Japan

• Takano Katsura

  Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Japan

• Kitao Yasuko

  Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Japan CREST, JST (Japan Science and Technology), Japan

• Hibino Satoshi

  Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Japan

• Choshi Tominari

  Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Japan

• Murakami Rika

  Meiji Dairies Corporation, Japan

• Suzuki Hiroto

  Meiji Dairies Corporation, Japan

• Yamada Masashi

  Taiho Pharmaceutical Co., Ltd., Japan

• Ogawa Satoshi

  Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Japan CREST, JST (Japan Science and Technology), Japan

• Hori Osamu

  Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Japan CREST, JST (Japan Science and Technology), Japan

Bibliographic Information

Other Title

• A carbazole derivative protects cells against endoplasmic reticulum stress and glutathione depletion

Abstract

Enhanced levels of intracellular stresses such as oxidative stress and endoplasmic reticulum (ER) stress are implicated in various neuropathological conditions including brain ischemia and neurodegeneration. During a search for compounds that regulate ER stress and ER stress-induced cell death, we identified a carbazole derivative 16-14 [9-(3-cyanobenzyl)-1,4-dimethylcarbazole] that protected against both ER stress and glutathione depletion. 16-14 suppressed tunicamycin (Tm)-induced cell death in both F9 Herp KO cells and PC12 cells, and its regulation of ER stress was associated with reduced levels of unfolded protein response (UPR) signaling. ER stress caused by overexpression of a fluorescent ER-resident protein, GFP-KDEL, was also attenuated by 16-14 without altering the expression levels of GFP-KDEL. 16-14 also prevented glutathione depletion-induced cell death caused by buthionine sulfoximine (BSO), but not likely via its anti-oxidative activity. Further analysis revealed that 16-14 suppressed increases in intracellular Ca²⁺ in response to thapsigargin (Tg). These results suggest that 16-14 may protect cells against different stresses via the maintenance of intracellular Ca²⁺ homeostasis.<br> [Supplementary Fig. 1: available only at http://dx.doi.org/10.1254/jphs.08136FP]<br>

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 108 (2), 164-171, 2008

  The Japanese Pharmacological Society

Keywords

• neuronal cell death
• stress response
• endoplasmic reticulum (ER)
• glutathione
• neuroprotection

Details

• CRID: 1390282680154787456
• NII Article ID: 10024384874
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.08136fp
• COI: 1:CAS:528:DC%2BD1cXhtlehsrfJ
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 9684766
• PubMed: 18845913
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9684766
• Web Site: https://search.jamas.or.jp/link/ui/2009106661
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed