Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin alpha conjugate of skin.
The inhibitory properties of phosphorylated cystatin alpha (P-cystatin alpha) and a conjugated protein of the P-cystatin alpha with filaggrin linker segment peptide (FLSP) against the growth of Staphylococcus bacteria and poliovirus were investigated. Both the P-cystatin alpha and the conjugated protein (P-cystatin alpha-FLSP conjugate) as a model for the cornified envelope of skin inhibited the cysteine protease activity of Staphylococcus aureus V8. The protease activity was inhibited by normal cornified envelope of newborn rat skin, which contains P-cystatin alpha, and P-cystatin alpha in cornified envelope of newborn rat skin also suppressed the growth of S. aureus V8. When P-cystatin alpha or P-cystatin alpha-FLSP conjugate was added to cultured HeLa cells infected with poliovirus, 50-70% of the cell-death due to poliovirus infection was prevented. The poliovirus 3C protease activity in the infected HeLa cells was inhibited by P-cystatin alpha or P-cystatin alpha-FLSP conjugate. As a result, the processing of viral capsid peptides was suppressed. These findings suggest that P-cystatin alpha and P-cystatin alpha-FLSP conjugate could play the role of the barrier against microorganism infections due to inhibition of their cysteine protease activities.
Takahashi
M
M
Department of Dermatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Tezuka
T
T
Korant
B
B
Katunuma
N
N
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D015891:Cystatins / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004817:Epidermis / Q000502:physiology; D000091344:Filaggrin Proteins; D006367:HeLa Cells; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D017955:Poliovirus / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012879:Skin Physiological Phenomena; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects
C070572:Csta protein, rat; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D010446:Peptide Fragments