Biosynthesis of Endogenous Cardiac Glycosides by Mammalian Adrenocortical Cells: Three Steps Forward

Hamlyn, John M.

doi:10.1373/clinchem.2003.029017

Cited by 21 publications

(13 citation statements)

References 14 publications

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“…As mentioned in the Introduction, CS-like compounds, including ouabain and bufalin derivatives, are present in many mammalian tissues, are synthesized by and secreted from the adrenal gland, and are considered a new family of steroid hormones (9,13,20). Thus, the effects of CS described here may represent physiological regulations of intracellular membrane traffic.…”

Section: Discussionmentioning

confidence: 99%

Role of endosomal Na⁺-K⁺-ATPase and cardiac steroids in the regulation of endocytosis

Feldmann¹,

Glukmann²,

Medvenev³

et al. 2007

American Journal of Physiology-Cell Physiology

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Plasma membrane Na(+)-K(+)-ATPase, which drives potassium into and sodium out of the cell, has important roles in numerous physiological processes. Cardiac steroids (CS), such as ouabain and bufalin, specifically interact with the pump and affect ionic homeostasis, signal transduction, and endocytosed membrane traffic. CS-like compounds are present in mammalian tissues, synthesized in the adrenal gland, and considered to be new family of steroid hormones. In this study, the mechanism of Na(+)-K(+)-ATPase involvement in the regulation of endocytosis is explored. We show that the effects of various CS on changes in endosomal pH are mediated by the pump and correspond to their effects on endosomal membrane traffic. In addition, it was found that CS-induced changes in endocytosed membrane traffic were dependent on alterations in [Na(+)] and [H(+)] in the endosome. Furthermore, we show that various CS differentially regulate endosomal pH and membrane traffic. The results suggest that these differences are due to specific binding characteristics. Based on our observations, we propose that Na(+)-K(+)-ATPase is a key player in the regulation of endosomal pH and endocytosed membrane traffic. Furthermore, our results raise the possibility that CS-like hormones regulate differentially intracellular membrane traffic.

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Section: Discussionmentioning

confidence: 99%

Role of endosomal Na⁺-K⁺-ATPase and cardiac steroids in the regulation of endocytosis

Feldmann¹,

Glukmann²,

Medvenev³

et al. 2007

American Journal of Physiology-Cell Physiology

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“…ouabain, digoxin, bufadienolides), cholesterol derivatives which can have both rapid (through interaction with the sodium/potassium-ATPase) and long-term (through the induction of gene expression and cell proliferation) effects on ionoregulation and cardiovascular function (Schoner 2002). Although their biosynthetic pathways have not been fully elucidated (Hamlyn 2004), there is evidence that several enzymes (including SCC) may be common to the synthesis of some cardiac glycosides and corticosteriods (Hamlyn et al 2003). However, the synthesis of bufadienolide in mammals appears to be independent of both StAR and SCC, as indicated by studies using mouse Y-1 adrenocortical cells transfected with genes that inhibit the expression of StAR and SCC (Dmitrieva et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Cloning and characterization of cDNAs encoding steroidogenic acute regulatory protein from freshwater stingrays (Potamotrygon spp.)

Nunez¹,

Piermarini²,

Evans³

et al. 2005

Journal of Molecular Endocrinology

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The steroidogenic acute regulatory protein (StAR) is critical to the regulated synthesis of steroids in vertebrates. We have isolated cDNA sequences encoding StAR in the freshwater stingrays Potamotrygon hystrix and P. motoro. A single P. hystrix StAR transcript (3376 bp) and two overlapping P. motoro StAR transcripts (1272 and 3365 bp) were isolated. The P. hystrix and P. motoro StAR transcripts contain open reading frames encoding proteins of 284 amino acids that are 99% identical to each other and 56-64% identical to other StAR proteins. Pregnenolone synthesis by green monkey kidney (COS-1) cells transfected with an expression construct encoding a human cholesterol side chain cleavage/adrenodoxin reductase/adrenodoxin fusion protein was increased 16-fold by coexpression with a pCMV5/P. motoro StAR expression construct. Northern blot analysis revealed a single 4000 bp StAR transcript in the P. motoro interrenal gland, but RT-PCR indicates StAR mRNA is also expressed in the brain, gonads, atria, ventricle, gill (female only) and muscle (female only). Expression in extragonadal and extraadrenocortical tissues is an indication that StAR may be critical to processes other than steroidogenesis. The longest P. motoro StAR transcript contains a sequence with great similarity to short interspersed repetitive elements found in other elasmobranchs. This study is the first to isolate and characterize elasmobranch StAR cDNA sequences and to demonstrate the activity of a nonmammalian StAR protein in a heterologous expression system.

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“…Using this methodology, the biosynthesis of DLC has been shown to follow the pathway described above: DLC biosynthesis utilizes cholesterol and progesterone as precursors and is attenuated by P450scc and 3βHSD inhibitors (Hamlyn et al, 2003;Hamlyn et al, 1998;Lichtstein et al, 1998;Qazzaz et al, 2004). As indicated previously (Hamlyn, 2004), only two major enzyme reactions may be necessary for the conversion of pregnenolone or progesterone to the simplest DLC: the inversion of the configuration at carbons 5 and 14 (to form the cis-trans-cis configuration) and the addition of a lactone ring at carbon 17. The enzymes mediating these transformations are not known.…”

Section: Dlc Biosynthesis and Releasementioning

confidence: 96%

The digitalis-like steroid hormones: New mechanisms of action and biological significance

Nesher¹,

Shpolansky²,

et al. 2007

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Biosynthesis of Endogenous Cardiac Glycosides by Mammalian Adrenocortical Cells: Three Steps Forward

Cited by 21 publications

References 14 publications

Role of endosomal Na⁺-K⁺-ATPase and cardiac steroids in the regulation of endocytosis

Role of endosomal Na⁺-K⁺-ATPase and cardiac steroids in the regulation of endocytosis

Cloning and characterization of cDNAs encoding steroidogenic acute regulatory protein from freshwater stingrays (Potamotrygon spp.)

The digitalis-like steroid hormones: New mechanisms of action and biological significance

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Biosynthesis of Endogenous Cardiac Glycosides by Mammalian Adrenocortical Cells: Three Steps Forward

Cited by 21 publications

References 14 publications

Role of endosomal Na+-K+-ATPase and cardiac steroids in the regulation of endocytosis

Role of endosomal Na+-K+-ATPase and cardiac steroids in the regulation of endocytosis

Cloning and characterization of cDNAs encoding steroidogenic acute regulatory protein from freshwater stingrays (Potamotrygon spp.)

The digitalis-like steroid hormones: New mechanisms of action and biological significance

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Product

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Role of endosomal Na⁺-K⁺-ATPase and cardiac steroids in the regulation of endocytosis

Role of endosomal Na⁺-K⁺-ATPase and cardiac steroids in the regulation of endocytosis