Role of melittin-like region within phospholipase A2-activating protein in biological function

Deborah A. Ribardo, Kristine R. Kuhl, Johnny Peterson, Ashok Chopra

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Phospholipase A2-activating protein (PLAA) has been implicated in the production of prostaglandins (e.g. PGE2) via activation of phospholipases in various stimulated cell types. Human PLAA, with 738 amino acid (aa) residues, contains a region of 38% homology (aa 503-538) with the 26-aa long melittin peptide, a major component of bee venom and a reported regulator of phospholipase A2 and phospholipase D activity. To learn more about the role of PLAA in the production of eicosanoids and other inflammatory mediators, we synthesized a murine PLAA peptide (36-aa long) having homology to melittin, as well as to human and rat PLAA. The PLAA peptide and melittin increased the expression of genes encoding the proinflammatory cytokine tumor necrosis factor alpha (TNFα) and cyclooxygenase-2 (COX-2), which is involved in PGE2 production. We determined that the C-terminal region of the PLAA peptide (aa 515-538) was essential, since truncation of the C-terminal end of the PLAA peptide significantly reduced expression of genes encoding TNFα and COX-2 in macrophages. We concluded that PLAA could be important in the regulation of the inflammatory response because of its stimulatory effects on eicosanoid and cytokine synthesis. Consequently, control of plaa gene expression could be a target for the development of new drugs to control the inflammatory response.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalToxicon
Volume40
Issue number5
DOIs
StatePublished - 2002

Fingerprint

Melitten
Amino Acids
Peptides
Gene encoding
Eicosanoids
Cyclooxygenase 2
Gene Expression
Dinoprostone
Tumor Necrosis Factor-alpha
Cytokines
Bee Venoms
phospholipase A2-activating protein
Phospholipase D
Phospholipases
Macrophages
Drug and Narcotic Control
Phospholipases A2
Gene expression
Prostaglandins
Chemical activation

Keywords

  • Cyclooxygenase-2
  • Melittin
  • Phospholipase A-activating protein
  • Prostaglandins
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Toxicology

Cite this

Role of melittin-like region within phospholipase A2-activating protein in biological function. / Ribardo, Deborah A.; Kuhl, Kristine R.; Peterson, Johnny; Chopra, Ashok.

In: Toxicon, Vol. 40, No. 5, 2002, p. 519-526.

Research output: Contribution to journalArticle

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