Pepsin-mediated processing of the cytoplasmic histone H2A to strong antimicrobial peptide buforin I

Sik Kim Hun Sik Kim, H. Yoon, I. Minn, C. B. Park, Taek Lee Won Taek Lee, M. Zasioff, Chang Kim Sun Chang Kim

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


The intestinal epithelium forms a first line of innate host defense by secretion of proteins with antimicrobial activity against microbial infection. Despite the extensive studies on the antimicrobial host defense in many gastrointestinal tracts, little is known about the antimicrobial defense system of the stomach. The potent antimicrobial peptide buforin I, consisting of 39 aa, was isolated recently from the stomach tissue of an Asian toad, Bufo bufo gargarizans. In this study we examined the mechanism of buforin I production in toad stomach tissue. Buforin I is produced by the action of pepsin isozymes, named pepsin Ca and Cb, cleaving the Tyr39-Ala4°bond of histone H2A. Immunohistochemical analysis revealed that buforin I is present extracellularly on the mucosal surface, and unacetylated histone H2A, a precursor of buforin I, is localized in the cytoplasm of gastric gland cells. Furthermore, Western blot analysis showed that buforin I is also present in the gastric fluids, and immunoelectron microscopy detected localization of the unacetylated histone H2A in the cytoplasmic granules of gastric gland cells. The distinct subcellular distribution of the unacetylated histone H2A and the detection of the unacetylated buforin I both on the mucosal surface and in the lumen suggest that buforin I is produced from the cytoplasmic unacetylated histone H2A secreted into the gastric lumen and subsequently processed by pepsins. Our results indicate that buforin I along with pepsins in the vertebrate stomach may contribute to the innate host defense of the stomach against invading microorganisms.

Original languageEnglish (US)
Pages (from-to)3268-3274
Number of pages7
JournalJournal of Immunology
Issue number6
StatePublished - Sep 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Pepsin-mediated processing of the cytoplasmic histone H2A to strong antimicrobial peptide buforin I'. Together they form a unique fingerprint.

Cite this