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

FEBS Letters
JangJa HongKazuo Ohuchi

Abstract

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.

References

Feb 1, 1991·Trends in Pharmacological Sciences·N Nelson
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·E J BowmanK Altendorf
Oct 17, 1966·Biochimica Et Biophysica Acta·P WlodawerL Wojtczak
Nov 30, 1993·Biochemical and Biophysical Research Communications·B van HilleG Bilbe
Dec 24, 1997·Annals of the New York Academy of Sciences·D J KeelingL Sölvell
Oct 15, 1998·The Journal of Pathology·T OhtaS Ohkuma
Aug 10, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·H WieczorekW R Harvey
Feb 12, 2002·Nature Reviews. Molecular Cell Biology·Tsuyoshi Nishi, Michael Forgac
Feb 23, 2002·Planta medica·Kouya YamakiKazuo Ohuchi
Aug 21, 2002·The Journal of Biological Chemistry·Markus HussHelmut Wieczorek
Aug 26, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alfons Lawen
Nov 8, 2003·The Journal of Pharmacy and Pharmacology·JangJa HongKazuo Ohuchi
Dec 18, 2003·Chemistry : a European Journal·K C NicolaouParaskevi Giannakakou
Mar 5, 2004·The Journal of Biological Chemistry·Xiao-Song XieJef K De Brabander
Aug 6, 2005·BMC Biochemistry·Markus HussHelmut Wieczorek

❮ Previous
Next ❯

Citations

Aug 10, 2011·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Kavitha Priya KettimuthuAnup Ramachandran
Feb 6, 2015·International Journal of Clinical Oncology·Pengfei LiuWeidong Shen
Sep 14, 2012·Biological & Pharmaceutical Bulletin·You Jung Kim
Nov 29, 2011·The Journal of Organic Chemistry·Sanjay S PalimkarHiromi Ii
Nov 8, 2018·Organic & Biomolecular Chemistry·Tapas R Pradhan, Debendra K Mohapatra
Jun 24, 2016·Physiological Reviews·Laura StranskyMichael Forgac
Nov 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jong-Seok KimByung-Doo Hwang
Aug 17, 2010·Organic Letters·Sanjay S Palimkar, Jun'ichi Uenishi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Glycosides

Cardiac glycosides are a diverse family of naturally derived compounds that bind to and inhibit na+/k+-atpase. Discover the latest research on cardiac glycosides heres.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.