Glucosamine Research Today is a free monthly online journal that collates and summarizes the latest research about Glucosamine, including details on chondroitin sulfate, uses, effects, benefits, arthritis.

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.

Hong J, Yokomakura A, Nakano Y, Ishihara K, Kaneda M, Onodera M, Nakahama K, Morita I, Niikura K, Ahn JW, Zee O, Ohuchi K

Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Sendai, Miyagi 980-8578, Japan.

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.

Published 9 May 2006 in FEBS Lett, 580(11): 2723-30.
Full-text of this article is available online (may require subscription).

© 2004-2008 Glucosamine Research Today. All Rights Reserved.