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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ouabain shows high binding ability to myocardial Na+,K(+)-ATPase and, therefore, a suitably radiolabeled derivative of this compound may find use in myocardial imaging. In this pilot experiment we report the preparation of several chloroacetylated and iodoacetylated ouabagenins. These intermediates may possess the potential for conversion to 99mTc-labeled tracer by a reported procedure with which the imaging of myocardial Na+,K(+)-ATPase may be possible. Appropriate analytical and spectroscopic data for these intermediates are reported for the first time. To determine the stability of the iodoacetylated ouabagenins, corresponding 131I derivatives were synthesized which showed sufficient stability for incorporating a suitable radiometal-binding chelating moiety to these steroid molecules.
Steroids 1995 Jun
PMID:Iodoacetylated ouabagenins: their syntheses, spectroscopic characterizations, and stability studies. 767 82

Many mammalian tissues contain cardiac glycoside-like steroids that inhibit the sodium pump. A ouabain-like compound has been described in the human circulation and suggested to be ouabain or a closely related isomer. Ouabain is a highly hydroxylated compound and one of the most potent inhibitors of the sodium pump. Trialkylsilyl derivatization of ouabain has been carried out to determine reagent selectivity among the eight hydroxy groups as a prelude to the synthesis of regiospecific isomers. Mono-, di-, tri-, and hexa-trialkylsilyl derivatives have been prepared with substitution at the 19-, the 3',19-, the 1,3',19-, and the 1,2',3',4',11, 19-positions, respectively. Mass spectrometry and NMR confirmed the substitutions. Selective protection of the hydroxy groups allows selective oxidation of the unprotected steroid ring alcohols without oxidation of the 2'- and 4'-rhamnoside alcohols. Pyridinium dichromate oxidation of the di-trialkylsilyl and tri-trialkylsilyl derivatives gave the 1,11-diketone and the 11-ketone analogues, respectively. These regioselective reactions open a route to the synthesis of a series of closely related isomers of ouabain and other derivatives that may have useful structure-activity relationships and utility in the elucidation of the biosynthesis of ouabain-like compounds.
Steroids 2000 Jul
PMID:Regioselective derivatization of ouabain with trialkylsilyl reagents and selective oxidation of the unprotected alcohols. 1089 37

Progesterone acts at a plasma membrane receptor on the Rana oocyte to initiate meiosis. A cascade of lipid messengers occurs within seconds, followed by sequential changes in membrane phospholipid composition. We now show that progesterone binding to the plasma membrane increases continuously over the first 4 h. Subsequently, about 60% of the total plasma membrane and > 90% of membrane-bound progesterone, ouabain binding sites, and Na/K-ATPase activity are internalized. Until the completion of membrane internalization, oocytes must be continuously exposed to nanomolar concentrations of exogenous progesterone for meiosis to continue. The membrane-bound progesterone remains unchanged, whereas microinjected [(3)H]progesterone is rapidly metabolized. We find that progesterone and the plant steroid ouabain compete for one of two ouabain binding sites on the oocyte surface. Ouabain blocks progesterone action and inhibits subsequent meiosis if added at any time during the first 4-5 h. Western blots of SDS/PAGE extracts of isolated oocyte plasma membranes contain a -110 kDa band which binds an antibody to the steroid-binding c-terminal domain in rat and human PR. The number of binding sites and K(d) for progesterone binding to the plasma membrane is comparable to those for low-affinity ouabain binding to the alpha-subunit of the Na/K-ATPase (112 kDa). Our results suggest that progesterone binding to the ouabain binding site on the N-terminal region of the alpha-subunit of Na/K-ATPase may modulate early plasma membrane events over the first 4-6 h. Progesterone may thus act in part through the plasma membrane Na/K-ATPase signaling system.
Steroids 2005 Dec 15
PMID:The steroid-binding subunit of the Na/K-ATPase as a progesterone receptor on the amphibian oocyte plasma membrane. 1616 76

The steroid Na(+)/K(+) ATPase (NKA) blocker ouabain has been shown to exhibit pro-apoptotic effects in various cell systems; however, the mechanism involved in those effects is unclear. Here, we have demonstrated that incubation of HeLa cells during 24h with nanomolar concentrations of ouabain or digoxin causes apoptotic death of 30-50% of the cells. Ouabain caused the activation of caspases-3/7 and -9; however, caspase-8 was unaffected. The fact that compound Z-LEHD-FMK reduced both apoptosis and caspase-9 activation elicited by ouabain, suggest a mitochondrially-mediated pathway. This was strengthened by the fact that ouabain caused ATP depletion and the release of mitochondrial cytochrome c into the cytosol. Furthermore, upon ouabain treatment mitochondrial disruption and redistribution into the cytosol were observed. A mitochondrial site of action for ouabain was further corroborated by tight co-localisation of fluorescent ouabain with mitochondria. Finally, in ouabain-treated cells the histamine-elicited elevation of cytosolic Ca(2+) concentration ([Ca(2+)]c) suggests an additional effect on the endoplasmic reticulum (ER) leading to Ca(2+) store depletion. We conclude that fluorescent ouabain is taken up and tightly co-localises with mitochondria of HeLa cells. This indicates that apoptosis may be triggered by a direct action of ouabain on mitochondria.
Steroids 2013 Nov
PMID:Nanomolar ouabain elicits apoptosis through a direct action on HeLa cell mitochondria. 2393 21