GS28 protects neuronal cell death induced by hydrogen peroxide under glutathione-depleted condition

Hwa Ok Lee, Yu Jeong Byun, Kyung Ok Cho, Seong Yun Kim, Seong Beom Lee, Ho Shik Kim, Oh Joo Kwon, Seong Whan Jeong

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Golgi SNAP receptor complex 1 (GS28) has been implicated in vesicular transport between intra-Golgi networks and between endoplasmic reticulum (ER) and Golgi. Additional role(s) of GS28 within cells have not been well characterized. We observed decreased expression of GS28 in rat ischemic hippocampus. In this study, we examined the role of GS28 and its molecular mechanisms in neuronal (SK-N-SH) cell death induced by hydrogen peroxide (H 2O2). GS28 siRNA-transfected cells treated with H 2O2 showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, which corresponded to an increase of intracellular reactive oxygen species (ROS) in the cells. Pretreatment of GS28 siRNA-transfected cells with p38 chemical inhibitor significantly inhibited cytotoxicity; we also observed that p38 was activated in the cells by immunoblot analysis. We confirmed the role of p38 MAPK in cotransfected cells with GS28 siRNA and p38 siRNA in the cell viability assay, flow cytometry, and immunoblot. Involvement of apoptotic or autophagic processes in the cells was not shown in the cell viability, flow cytometry, and immunoblot analyses. However, pretreatment of the cells with necrostatin-1 completely inhibited H2O2-induced cytotoxicity, ROS generation, and p38 activation, indicating that the cell death is necroptotic. Collectively these data imply that H2O2 induces necroptotic cell death in the GS28 siRNA-transfected cells and that the necroptotic signals are mediated by sequential activations in RIP1/p38/ROS. Taken together, these results indicate that GS28 has a protective role in H 2O2-induced necroptosis via inhibition of p38 MAPK in GSH-depleted neuronal cells.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalKorean Journal of Physiology and Pharmacology
Volume15
Issue number3
DOIs
StatePublished - Jun 1 2011

Keywords

  • GS28
  • Glutathione
  • Hydrogen peroxide
  • MAPK
  • Necroptosis

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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    Lee, H. O., Byun, Y. J., Cho, K. O., Kim, S. Y., Lee, S. B., Kim, H. S., Kwon, O. J., & Jeong, S. W. (2011). GS28 protects neuronal cell death induced by hydrogen peroxide under glutathione-depleted condition. Korean Journal of Physiology and Pharmacology, 15(3), 149-156. https://doi.org/10.4196/kjpp.2011.15.3.149