p38 MAPK activation and mitochondrial depolarization mediate the cytotoxicity of Taiwan cobra phospholipase A2 on human neuroblastoma SK-N-SH cells

Ku Chung Chen, Pei Hsiu Kao, Shinne Ren Lin, Long Sen Chang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Modification of catalytic residue His-47 with p-bromophenacyl bromide (BPB) abolished the enzymatic activity of Naja naja atra phospholipase A2 (PLA2). Additionally, alterations in the global structure and the spatial positions of Trp residues were noted in His-modified PLA2. The cell viability of human neuroblastoma SK-N-SH cells was decreased by approximately 40% and 20% after treatment with 10 μM PLA2 and BPB-PLA2, respectively. Native and His-modified PLA2 induced a necrotic cell death accompanied with an activation of p38 MAPK, the loss of mitochondrial membrane potential (ΔΨm) and cytochrome c release. Pretreatment with SB202190 (p38 MAPK inhibitor) and cyclosporine A (inhibitor of mitochondria permeability transition pore) rescued cell viability, ΔΨm and cytochrome c release of PLA2-treated cells. Taken together, our data indicate that PLA2 activity does not play an indispensable role on the cytotoxicity of N. naja atra PLA2, and suggest a novel function of secretory PLA2 in inducing cell death of neuroblastoma. Moreover, the reduced cytotoxicity noted with BPB-PLA2 may be partly attributed to conformational distortion after modification of His-47.

Original languageEnglish
Pages (from-to)53-58
Number of pages6
JournalToxicology Letters
Volume180
Issue number1
DOIs
Publication statusPublished - Jul 30 2008
Externally publishedYes

Keywords

  • Conformational distortion
  • Cytotoxicity
  • Mitochondrial depolarization
  • Modification of histidine
  • p38 MAPK activation
  • Phospholipase A

ASJC Scopus subject areas

  • Toxicology

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