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Inhibition of vacuolar‐type (H + )‐ATPase by the cytostatic macrolide apicularen A and its role in apicularen A‐induced apoptosis in RAW 264.7 cells
Author(s) -
Hong JangJa,
Yokomakura Aya,
Nakano Yasuhiro,
Ishihara Kenji,
Kaneda Makoto,
Onodera Mitsue,
Nakahama Ken-ichi,
Morita Ikuo,
Niikura Kazuaki,
Ahn Jong-Woong,
Zee OkPyo,
Ohuchi Kazuo
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.04.031
Subject(s) - bafilomycin , acridine orange , atpase , atp hydrolysis , intracellular , chemistry , v atpase , biochemistry , apoptosis , nigericin , acridine , vacuole , microbiology and biotechnology , biology , enzyme , cytoplasm , membrane , organic chemistry , autophagy
Apicularen A and the known vacuolar‐type (H + )‐ATPase (V‐ATPase) inhibitor bafilomycin A 1 induced apoptosis of RAW 264.7 cells, while apicularen B, an N ‐acetyl‐glucosamine glycoside of apicularen A, was far less effective. Apicularen A inhibited vital staining with acridine orange of the intracellular organelles of RAW 264.7 cells, inhibited the ATP‐dependent proton transport into inside‐out microsome vesicles, and inhibited the bafilomycin A 1 ‐sensitive ATP hydrolysis. The IC 50 values of the proton transport were 0.58 nM for apicularen A, 13 nM for apicularen B, and 0.95 nM for bafilomycin A 1 . Furthermore, apicularen A inhibited the bafilomycin A 1 ‐sensitive ATP hydrolysis more potently than apicularen B. F‐ATPase and P‐ATPase were not inhibited by apicularen A. We concluded that apicularen A inhibits V‐ATPase, and thus induces apoptosis in RAW 264.7 cells.