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Clinical Chemistry 42: 1092-1099, 1996;
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Clinical Chemistry, Vol 42, 1092-1099, Copyright © 1996 by American Association for Clinical Chemistry

Evidence for presence of a reduced form of digoxin-like immunoreactive factor (dihydro-DLIF) in mammalian tissues

HM Qazzaz, SA Jortani, JM Poole and R Valdes Jr
Department of Pathology, University of Louisville School of Medicine, KY 40292, USA.

Digoxin-like immunoreactive factor (DLIF) from adrenal glands is an endogenous ligand structurally related to the plant-derived cardiac glycoside digoxin. Cardiac glycosides regulate the activity of the sodium pump and thus play key roles in disease processes involving regulation of ion transport. We now report the discovery of an endogenous dihydro-DLIF analogous to dihydrodigoxin. We used HPLC, ultraviolet spectrophotometry, and cross-reactivity with two antibodies, one specific for digoxin and one for dihydrodigoxin, to support the hypothesis that dihydro-DLIF contains a chemically reduced lactone ring. The spectral absorbance maximum for dihydro-DLIF is at 196 nm, identical to dihydrodigoxin. DLIF and dihydro-DLIF are 975- and 2588-fold less immunoreactive than digoxin and dihydrodigoxin for their respective antibodies. The molar ratio of dihydro-DLIF to DLIF is approximately 5.3 in bovine adrenocortical tissue and approximately 0.38 in human serum. Dihydrodigoxin (reduced lactone ring) added to microsomes isolated from bovine adrenal cortex produced a 4.5-fold increase in digoxin-like immunoreactivity (oxidized lactone ring) after 3 h of incubation. The biotransformation is likely mediated by a cytochrome P-450 NADPH-dependent process. Our findings demonstrate the presence of a dihydro-DLIF in mammals and suggest a metabolic route for synthesis of endogenous DLIF in mammalian tissue.


The following articles in journals at HighWire Press have cited this article:


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 Clin. Chem.Home page
K. Ihenetu, H. M. Qazzaz, F. Crespo, R. Fernandez-Botran, and R. Valdes Jr
Digoxin-Like Immunoreactive Factors Induce Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia
Clin. Chem., July 1, 2007; 53(7): 1315 - 1322.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
S. A. Jortani, S. D. Prabhu, and R. Valdes Jr
Strategies for Developing Biomarkers of Heart Failure
Clin. Chem., February 1, 2004; 50(2): 265 - 278.
[Abstract] [Full Text] [PDF]


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Copyright © 1996 by the American Association for Clinical Chemistry.