Marinobufagenin (marinobufagin, MBG) is a

cardiotonic A cardiac stimulant is a drug which acts as a stimulant of the heart – e.g., via Chronotropic#Positive chronotropes, positive chronotropic action (increased heart rate) and/or Inotrope#Positive inotropic agents, inotropic action (increased myocar ...

bufadienolide Bufadienolide is a chemical compound with steroid structure. Its derivatives are collectively known as bufadienolides, including many in the form of bufadienolide glycosides (bufadienolides that contain structural groups derived from sugars). These ...

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

. It is secreted by the

toad Toad (also known as a hoptoad) is a common name for certain frogs, especially of the family Bufonidae, that are characterized by dry, leathery skin, short legs, and large bumps covering the parotoid glands. In popular culture (folk taxonomy ...

species such as ''

Bufo marinus The cane toad (''Rhinella marina''), also known as the giant neotropical toad or marine toad, is a large, terrestrial true toad native to South and mainland Central America, but which has been introduced to various islands throughout Oceania ...

''. It also can be found in the plasma and urine of human subjects with myocardial infarction, kidney failure, heart failure, and preeclampsia. MBG is a

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

and a sodium–potassium adenosine triphosphatase (Na/K-ATPase) inhibitor with a high affinity for the alpha-1 isoform of the enzyme, the main isoform in the vascular wall and the kidney. It is produced by adrenal cortex and placenta via CYP27a1 pathway. MBG regulates the monovalent ions balance and cell homeostasis, and by binding to the Na/K-ATPase, it affects cell growth and differentiation, apoptosis, and proliferation. A novel effect of MBG is their ability to induce intracellular signaling, leading to a loss of elasticity and vascular fibrosis. One of the mechanisms of the pro-fibrotic effect of MBG is the inhibition of the activity of Fli1, a nuclear transcription factor and a negative regulator of collagen 1 synthesis. Fli1 competes with another transcription factor, ETS-1, to maintain a balance between stimulation and repression of the collagen-1 gene. The Na/K ATPase/Src/EGFR complex emerges as a signal cascade, which activates phospholipase C, resulting in the phosphorylation of PKCδ and its translocation to the nucleus. In the nucleus, PKCδ phosphorylates Fli1, which withdraws the Fli1-induced inhibition of the collagen-1 promoter and increases procollagen expression and collagen production. The antagonism of the pressor and profibrotic effects of MBG by monoclonal anti-MBG antibodies may lead to the prevention of vascular fibrosis in patients with end-stage renal disease and preeclampsia.

References

Amphibian toxins Epoxides Bufanolides Diols Heterocyclic compounds with 5 rings {{biochem-stub