Efficient protection by cationized catalase against H2O2 injury in primary cultured alveolar epithelial cells.
Increasing evidence suggests that hydrogen peroxide plays an important role in alveolar epithelial injury produced during many inflammatory lung diseases. In this study, the successful prevention of hydrogen peroxide (H(2)O(2))-induced injury in primary cultured rabbit alveolar epithelial cells by cationized catalase is described. Cationized catalase was synthesized by direct chemical modification to enhance its association with alveolar epithelial cells. Cationized catalase exhibited a 22.3-fold higher cellular association at 2 h than native catalase, and incubation of cationized catalase with the cells produced a 2.19-fold intracellular catalase activity, which suggested that cationized catalase distributed both to the cell membrane and into the cell interior. Cationized catalase markedly suppressed H(2)O(2)-induced cell injury. In addition, electron spin resonance spectrometry analysis revealed that cationized catalase effectively eliminated H(2)O(2) produced in the medium by glucose plus glucose oxidase. On the other hand, polyethylene glycol-modified catalase (PEG-catalase) did not have any protective effect against H(2)O(2)-induced cell injury although PEG-catalase exhibited a 2.49-fold higher cellular association at 2 h than native catalase. These results suggest that cationization of catalase is a promising strategy for the treatment of many of inflammatory lung diseases.
Nemoto
Takayuki
T
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D002374:Catalase / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D005562:Formazans / Q000032:analysis; D006861:Hydrogen Peroxide / Q000633:toxicity; D007205:Indium Radioisotopes; D016877:Oxidants / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry; D020011:Protective Agents / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D013778:Tetrazolium Salts / Q000032:analysis
D005562:Formazans; D007205:Indium Radioisotopes; D016877:Oxidants; D020011:Protective Agents; D013778:Tetrazolium Salts; C079782:MTT formazan; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase