Biosynthesis of the bufadienolide marinobufagin in toadsBufo paracnemis from cholesterol-20-14C

Porto, A. M.; Gros, Eduardo G.

doi:10.1007/bf02147562

Cited by 35 publications

(23 citation statements)

References 6 publications

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“…Pregnenolone, the immediate product of side-chain cleavage, is not incorporated into amphibian BDs. Thus, pregnenolone is not a precursor to the production of MBG in Bufo paracnemis, 47,48 Bufo arenarum, 49 and Bufo marinus. 50 Cholesterol may be a precursor of BD biosynthesis in amphibians, and the conversion of cholesterol stably labeled in the steroid nucleus to BDs has been shown.…”

Section: Discussionmentioning

confidence: 92%

“…50 Cholesterol may be a precursor of BD biosynthesis in amphibians, and the conversion of cholesterol stably labeled in the steroid nucleus to BDs has been shown. 48,50 It is not clear whether cholesterol is a normal and obligatory constituent in the amphibian biosynthetic pathway, because no experiments interfering with the production of cholesterol and its effect on BD production have been reported. Lichtstein et al 4 have recently reported studies examining BDs in homogenates of mammalian AC cells.…”

Section: Discussionmentioning

confidence: 99%

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Mammalian Bufadienolide Is Synthesized From Cholesterol in the Adrenal Cortex by a Pathway That Is Independent of Cholesterol Side-Chain Cleavage

et al. 2000

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Abstract-An increasing body of evidence suggests that an endogenous mammalian bufadienolide (BD) may be involved in the regulation of Na ϩ ,K ϩ -ATPase activity and the pathogenesis of arterial hypertension. We developed a purification scheme for marinobufagenin (MBG), an amphibian cardiotonic BD, and applied it to purify and characterize material in human plasma, culture medium conditioned by Y-1 adrenocortical cells, and rat adrenal tissue. MBG immunoreactivity purified from plasma and measured by ELISA showed important similarities (chromatography and antibody cross-reactivity) to material secreted into cell culture medium by Y-1 cells. This observation indicates that circulating mammalian BD may have an adrenocortical origin. Release of mammalian BD from adrenocortical cells grown in the absence of exogenous cholesterol was reduced by treatment of cultures with mevastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Supplementation of the serum and cholesterol-free cell culture medium with the LDL fraction of human plasma increased the production of MBG material in the presence of mevastatin, supporting its origin from cholesterol. We used Y-1 cell lines transfected with genes shown to inhibit steroidogenesis through cholesterol side-chain cleavage (Y-1/DAX and Y-1/RIAB) to investigate the dependence of MBG biosynthesis on side-chain cleavage. Our results indicate that the mammalian BD is synthesized in the adrenal cortex from cholesterol and shares important similarities with the amphibian BD MBG, that its biosynthesis is independent of transfer of cholesterol to the side-chain cleavage enzyme complex mediated by steroidogenic acute regulatory protein, and that neither cAMP nor protein kinase A appears to be a critical component of the pathway controlling its biosynthesis.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Mammalian Bufadienolide Is Synthesized From Cholesterol in the Adrenal Cortex by a Pathway That Is Independent of Cholesterol Side-Chain Cleavage

et al. 2000

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“…De novo synthesis by the fireflies themselves seems unlikely, because the only available evidence indicates that insects are incapable of carrying out steroid biosynthesis from nonsteroidal precursors (25). The most reasonable hypothesis, therefore, is that the beetles produce the lucibufagins from ingested cholesterol, a process already demonstrated to account for bufadienolide synthesis in toads (26). Other defensive steroids of insects need not be produced by such endogenous transformation.…”

Section: Discussionmentioning

confidence: 98%

Lucibufagins: Defensive steroids from the fireflies Photinus ignitus and P. marginellus (Coleoptera: Lampyridae)

Eisner

Wiemer

Haynes

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

107

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Feeding tests with thrushes (Hylocichia spp.) led to the isolation of three novel steroid pyrones from fireflies (Photinus ignitus and P. marginellus) responsible, in part at least, for the unpalatability of these insects to the birds. The term lucibufagin is coined for these steroidal pyrones. The closest known relatives of lucibufagins are the familiar cardiotonic bufadienolides, found in certain toads and plants. It had previously been suspected that fireflies-the familiar luminescent beetles of the family Lampyridae-contain noxious substances that protect them against vertebrate predators. A diversity of lizards, birds, and mammals was said to reject these insects, but the defensive substances responsible, presumed to be present in the blood and tissues of the beetles, had not been characterized (2-4).Pursuant to our finding that fireflies of the genus Photinus are rejected by birds (thrushes of the genus Hylocichla), we developed a bioassay with these predators by which the feeding deterrency of extracts of Photinus, and that of fractions of the extracts, could be evaluated. The procedure led to the isolation of three novel steroidal pyrones, deterrent to the birds, and present in the beetles at defensively effective concentrations. We here describe the isolation and partial characterization of these compounds, for which we propose the term lucibufagins. Steroidal pyrones, or bufadienolides, are of restricted occurrence in nature. They have been found in some well-known toad venoms as well as in a small group of plants (ref. 5, pp. 469-476). However, no examples have been reported from invertebrates. MATERIALS AND METHODSThe two species of Photinus studied, P. ignitus and P. marginellus, are common in the northeastern United States. They were collected at night with nets in the environs of Ithaca, New York, and immediately brought to the laboratory for feeding tests or chemical extractions. Because the fireflies were taken in flight, they can be assumed to be virtually all males. Thrushes were chosen for the feeding tests because they adapted well to captivity and were known to be broadly insectivorous in their habits. A single Swainson's thrush (Hylocichla ustulata, male) and five hermit thrushes (H. guttata, three females and two males) were used. All had been taken months beforehand in mist nets during the migratory season. They were caged singly in the laboratory and were "experienced" at the time of experimentation, having previously been offered palatable and unpalatable insects in connection with other studies. They were sexed at autopsy.The initial tests with the single Swainson's thrush were in-The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 905tended to provide preliminary data on the food preferences of such a bird. These tests extended over a period of 23 days, during which the thrush was offered, in daily feedi...

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“…The cardiotonic steroids consist of bufogenins (bufadienolides) and bufotoxins (Zelnik, 1965;Meyer, 1966;Meyer and Linde, 1971;Lichtstein et al, 1992). Bufogenins and bufotoxins are synthesized by the toads from cholesterol (Doull et al, 1951;Siperstein et al, 1957;Meyer, 1966;Porto and Gros, 1971;Porto et al, 1972), and are cardiotoxic to some mammals (Toledo and Jared, 1995). Presumably, the precursors to these toxins are delivered to the gland by the blood, where they are converted into toxins within the secretory syncytia (Erspamer, 1994).…”

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confidence: 97%

Vasculature of the parotoid glands of four species of toads (bufonidae: bufo)

Hutchinson

Savitzky

2004

Journal of Morphology

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The parotoid glands of toads (Bufonidae) consist of large aggregations of granular glands located between the otic region of the skull and the scapular region. To determine the circulatory pattern of these glands, we perfused the vascular systems of Bufo alvarius, B. marinus, B. terrestris, and B. valliceps with either India ink or Microfil, a fine latex. The perfused glands were studied by gross dissection, microscopic examination, and histology. The vascular patterns of the parotoid glands were compared to the arrangement of vessels in the dorsal skin of Rana sphenocephala (Ranidae), a frog that lacks parotoid glands. The parotoid glands of the four species of toads are supplied with blood by the lateral and dorsal cutaneous arteries and are drained by one or more branches of the internal jugular vein. The dorsal cutaneous artery supplies most of the blood to the parotoid glands in B. terrestris and B. valliceps. In B. alvarius and B. marinus, both the lateral and dorsal cutaneous arteries serve major roles in the blood supply of the glands. These patterns of blood flow have not been described previously for parotoid glands and conflict with earlier accounts for B. alvarius and B. marinus. The arteries and veins associated with the parotoid glands of toads are present in R. sphenocephala, but are arranged differently. In R. sphenocephala, the lateral cutaneous artery supplies the dorsal and lateral skin posterior to the shoulder region, whereas the dorsal cutaneous artery supplies the skin of the shoulder region. In toads, both the lateral and dorsal cutaneous arteries supply the skin of the shoulder region and ramify into subcutaneous capillaries that surround the secretory units of the parotoid glands. Extensive vasculature presumably is important for delivering cholesterol and other precursor molecules to the parotoid glands, where those compounds are converted into toxins.

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Biosynthesis of the bufadienolide marinobufagin in toadsBufo paracnemis from cholesterol-20-14C

Cited by 35 publications

References 6 publications

Mammalian Bufadienolide Is Synthesized From Cholesterol in the Adrenal Cortex by a Pathway That Is Independent of Cholesterol Side-Chain Cleavage

Mammalian Bufadienolide Is Synthesized From Cholesterol in the Adrenal Cortex by a Pathway That Is Independent of Cholesterol Side-Chain Cleavage

Lucibufagins: Defensive steroids from the fireflies Photinus ignitus and P. marginellus (Coleoptera: Lampyridae)

Vasculature of the parotoid glands of four species of toads (bufonidae: bufo)

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