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
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Sendai, Miyagi 980-8578, Japan.
FEBS Lett. 2006 May 15;580(11):2723-30. doi: 10.1016/j.febslet.2006.04.031. Epub 2006 Apr 21.
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.
顶孢霉素A和已知的液泡型（H⁺）-ATP酶（V-ATP酶）抑制剂巴弗洛霉素A₁可诱导RAW 264.7细胞凋亡，而顶孢霉素A的N-乙酰葡糖胺糖苷顶孢霉素B的效果则差得多。顶孢霉素A抑制RAW 264.7细胞内细胞器的吖啶橙活体染色，抑制ATP依赖的质子转运到外翻微体小泡中，并抑制巴弗洛霉素A₁敏感的ATP水解。质子转运的IC₅₀值分别为：顶孢霉素A为0.58 nM，顶孢霉素B为13 nM，巴弗洛霉素A₁为0.95 nM。此外，顶孢霉素A比顶孢霉素B更有效地抑制巴弗洛霉素A₁敏感的ATP水解。F-ATP酶和P-ATP酶不受顶孢霉素A抑制。我们得出结论，顶孢霉素A抑制V-ATP酶，从而诱导RAW 264.7细胞凋亡。
