Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides.
Singlet oxygen is a causal factor in light-induced skin photoaging and the cytotoxic process of tumor cells in photodynamic chemotherapy. To develop a better understanding of the functional consequences of protein modification by singlet oxygen, the effects of naphthalene endoperoxide on lysosomal protease, cathepsin, were examined. When the soluble fraction of normal human fetal skin fibroblast cells was treated with the endoperoxide, the activities of cysteine proteases, cathepsins B and L/S, were inhibited, but that of aspartate protease, cathepsin D/E, was not. The reduction of the endoperoxide-treated soluble fractions by treatment with dithiothreitol barely recovered the activities. Cathepsin B, purified from normal human liver, exhibited similar profiles to that in cytosol. These data suggest that singlet oxygen oxidatively modifies an amino acid residue essential for catalysis and consequently results in the irreversible inactivation of cysteine protease-type cathepsin.
Nagaoka
Yuki
Y
Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Japan.
Otsu
Kaoru
K
Okada
Futoshi
F
Sato
Kazuaki
K
Ohba
Yoshihiro
Y
Kotani
Naoki
N
Fujii
Junichi
J
D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000737:chemistry / Q000494:pharmacology; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D010545:Peroxides / Q000737:chemistry / Q000494:pharmacology*; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism*
C114034:3-(4'-methyl-1'-naphthyl)propionic acid 1',4'-endoperoxide; D008054:Lipid Peroxides; D009281:Naphthalenes; D010545:Peroxides; D011422:Propionates; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C117474:naphthalene endoperoxide; D026082:Singlet Oxygen; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L