Archives of Pharmacal Research

, Volume 35, Issue 7, pp 1269–1278

The regulatory mechanism of 4-phenylbutyric acid against ER stress-induced autophagy in human gingival fibroblasts

Research Articles Drug Actions


Endoplasmic reticulum (ER) stress is closely connected to autophagy. When cells are exposed to ER stress, cells exhibit enhanced protein degradation and form autophagosomes. In this study, we demonstrate that the chemical chaperone, 4-phenylbutyric acid (4-PBA), regulates ER stressinduced cell death and autophagy in human gingival fibroblasts. We found that 4-PBA protected cells against thapsigargin-induced apoptotic cell death but did not affect the reduced cell proliferation. ER stress induced by thapsigargin was alleviated by 4-PBA through the regulation of several ER stress-inducible, unfolded protein response related proteins including GRP78, GRP94, C/EBP homologous protein, phospho-eIF-2α, eIF-2α, phospho-JNK1 (p46) and phospho-JNK2/3 (p54), JNK1, IRE-1α, PERK, and sXBP-1. Compared with cells treated with thapsigargin alone, cells treated with both 4-PBA and thapsigargin showed lower levels of Beclin-1, LC-3II and autophagic vacuoles, indicating that 4-PBA also inhibited autophagy induced by ER stress. This study suggests that 4-PBA may be a potential therapeutic agent against ER stress-associated pathologic situations.

Key words

Human gingival fibroblasts ER stress 4-Phenylbutyric acid 


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Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2012

Authors and Affiliations

  • Do-Sung Kim
    • 1
  • Bo Li
    • 1
  • Ki Yon Rhew
    • 2
  • Hyo-Won Oh
    • 3
  • Hyun-Dae Lim
    • 4
  • Wan Lee
    • 5
  • Han-Jung Chae
    • 1
  • Hyung-Ryong Kim
    • 6
    • 7
  1. 1.Department of Pharmacology and Institute of Cardiovascular Research, School of MedicineChonbuk National UniversityJeonju, ChonbukKorea
  2. 2.College of PharmacyDongduk Women’ UniversitySeoulKorea
  3. 3.Department of Public Oral Health and Preventive Dentistry, School of DentistryWonkwang UniversityIksan, ChonbukKorea
  4. 4.Department of Oral Medicine and Diagnosis, School of DentistryWonkwang UniversityIksan, ChonbukKorea
  5. 5.Department of Oral and Maxillofacial Radiology, School of DentistryWonkwang UniversityIksan, ChonbukKorea
  6. 6.Department of Dental Pharmacology and Wonkwang Biomaterial Implant Research Institute, School of DentistryWonkwang UniversityIksan, ChonbukKorea
  7. 7.Department of Dental Pharmacology and Wonkwang Dental Research Institute, School of DentistryWonkwang UniversityIksan, ChonbukKorea

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