Cathepsin D produces antimicrobial peptide parasin I from histone H2A in the skin mucosa of fish.
Parasin I is a potent 19-residue antimicrobial peptide isolated from the skin mucus of wounded catfish (Parasilurus asotus). Here we describe the mechanism of parasin I production from histone H2A in catfish skin mucosa on epidermal injury. Cathepsin D is found to exist in the mucus as an inactive proenzyme (procathepsin D), and a metalloprotease, induced on injury, cleaves procathepsin D to generate active cathepsin D. This activated form of cathepsin D then cleaves the Ser19-Arg20 bond of histone H2A to produce parasin I. Immunohistochemical analysis reveals that unacetylated histone H2A, a precursor of parasin I, and procathepsin D are present in the cytoplasm of epithelial mucous cells and that parasin I is produced on the mucosal surface on epidermal injury. Western blot analysis shows that parasin I is also present in the skin mucus of other fish species. Furthermore, parasin I shows good antimicrobial activity against fish-specific bacterial pathogens. Taken together, these results indicate that cathepsin D and a metalloprotease participate in the production of parasin I from histone H2A and that parasin I contributes to the innate host defense of the fish against invading microorganisms.
Cho
Ju Hyun
JH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305--701, Korea.
Park
In Yup
IY
Kim
Hun Sik
HS
Lee
Won Taek
WT
Kim
Mi Sun
MS
Kim
Sun Chang
SC
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D002397:Catfishes / Q000033:anatomy & histology / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism / Q000502:physiology*; D004792:Enzyme Precursors / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005393:Fish Diseases / Q000378:metabolism / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism; D016415:Sequence Alignment; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004792:Enzyme Precursors; D006657:Histones; D011498:Protein Precursors; C115701:parasin I; C058345:procathepsin D; D002402:Cathepsin D; D008666:Metalloendopeptidases