Abstract
Apicularens A and B were isolated from the myxobacterial genus Chondromyces apiculatus JW184. Apicularen A inhibited bafilomycin A1-sensitive ATP-dependent proton transport into microsome vesicles more potently than apicularen B. Bone resorption in cultures of mouse calvariae induced by human parathyroid hormone (PTH) or interleukin-1beta (IL-1beta) was inhibited by apicularen A at 10 and 100 nM, while apicularen B had no effect. The bisphosphonate incadronate inhibited bone resorption at 100 nM, being less effective than apicularen A. Our findings indicate that apicularen A inhibits bone resorption induced by PTH or IL-1beta more potently than apicularen B, probably due to inhibition of the V-ATPase.
MeSH terms
-
Animals
-
Bone Resorption*
-
Bridged Bicyclo Compounds, Heterocyclic / chemistry
-
Bridged Bicyclo Compounds, Heterocyclic / isolation & purification
-
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
-
Diphosphonates / chemistry
-
Diphosphonates / pharmacology
-
Humans
-
Macrolides / chemistry
-
Macrolides / isolation & purification
-
Macrolides / pharmacology
-
Mice
-
Myxococcales / chemistry*
-
Parathyroid Hormone / pharmacology
-
Skull / drug effects
-
Vacuolar Proton-Translocating ATPases / antagonists & inhibitors
Substances
-
Bridged Bicyclo Compounds, Heterocyclic
-
Diphosphonates
-
Macrolides
-
Parathyroid Hormone
-
apicularen A
-
apicularen B
-
cimadronate
-
bafilomycin A1
-
Vacuolar Proton-Translocating ATPases