Open AccessIdentification of digitalis‐like compounds in human cataractous lenses
Author(s) -
LICHTSTEIN David,
GATI Irith,
SAMUELOV Sarah,
BERSON David,
ROZENMAN Yaacov,
LANDAU Louis,
DEUTSCH Joseph
Publication year - 1993
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1993.tb18141.x
Subject(s) - chemistry , ouabain , chromatography , atpase , mass spectrometry , peptide , digitalis , digoxin , uv filter , size exclusion chromatography , biochemistry , enzyme , sodium , organic chemistry , medicine , heart failure , physics , optics
Human cataractous lens nuclei extract inhibited, in a dose‐dependent fashion, [ 3 H]ouabain binding to rat brain synaptosomes and microsomal Na + ‐ and K + ‐dependent adenosine triphosphate (Na + , K + ‐ATPase) activity and interacted with anti‐digoxin antibodies. The compounds responsible for these activities, termed digitalis‐like compounds (DLC), were also detected in bovine, rat, cat and rabbit, normal, transparent lenses, but the levels were only 0.7–5.4% of the average levels in the cataractous human lenses. DLC from the human cataractous lenses were purified by a procedure consisting of organic extractions and batch chromatography followed by filtration through a 3000 Da cut‐off filter and subsequent separations using reverse‐phase high‐performance liquid chromatography. The presence of DLC in the different fractions obtained in the chromatograms was monitored by their ability to inhibit [ 3 H]ouabain binding and Na + , K + ‐ATPase activity. Based on chemical ionization mass spectrometry together with ultraviolet spectrometry and biological characterization, it is suggested that new bufodienolides, 19‐norbufalin and 19‐norbufalin peptide derivatives are responsible for the endogenous DLC activity. It is proposed that these compounds may regulate Na + , K + ‐ATPase activity in the lens under some physiological and pathological conditions.