Wikipedia

Marinobufagenin

Marinobufagenin (marinobufagin, MBG) is a cardiotonic bufadienolide steroid.[1] It is secreted by the toad species such as Bufo marinus.[1]  It also can be found in the plasma and urine of human subjects with myocardial infarction, kidney failure, heart failure, and preeclampsia.[2][3][4][5] MBG is a vasoconstrictor 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.[6]

Marinobufagenin
Names
IUPAC name
3β,5-Dihydroxy-14,15-epoxy-5β,14β-bufa-20,22-dienolide
Systematic IUPAC name
5-[(1R,2aR,3aS,3bR,5aS,7S,9aR,9bS,11aR)-5b,7-Dihydroxy-9a,11a-dimethylhexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-1-yl]-2H-pyran-2-one
Other names
Marinobufagin, Marinobufagenin
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C24H32O5/c1-21-8-5-15(25)12-23(21,27)10-7-17-16(21)6-9-22(2)18(11-19-24(17,22)29-19)14-3-4-20(26)28-13-14/h3-4,13,15-19,25,27H,5-12H2,1-2H3/t15-,16-,17+,18+,19+,21+,22+,23-,24+/m0/s1 ☒N
    Key: JMNQTHQLNRILMH-OBBGIPBRSA-N ☒N
  • InChI=1/C24H32O5/c1-21-8-5-15(25)12-23(21,27)10-7-17-16(21)6-9-22(2)18(11-19-24(17,22)29-19)14-3-4-20(26)28-13-14/h3-4,13,15-19,25,27H,5-12H2,1-2H3/t15-,16-,17+,18+,19+,21+,22+,23-,24+/m0/s1
    Key: JMNQTHQLNRILMH-OBBGIPBRBU
  • C[C@]12CC[C@@H](C[C@]1(CCC3C2CC[C@]4([C@]35[C@H](O5)C[C@@H]4C6=COC(=O)C=C6)C)O)O
Properties
C24H32O5
Molar mass 400.515 g·mol−1
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Toxic
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

It is produced by adrenal cortex and placenta via CYP27a1 pathway.[7] 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.[8] A novel effect of MBG is their ability to induce intracellular signaling, leading to a loss of elasticity and vascular fibrosis.[9]

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.[10]

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.[11]

References

edit
  1. ^ a b Butler, VP Jr.; Morris, JF; Akizawa, T; et al. (1996). "Heterogeneity and lability of endogenous digitalis-like substances in the plasma of the toad, Bufo marinus". American Journal of Physiology. 271 (2): R325 – R332. doi:10.1152/ajpregu.1996.271.2.R325.
  2. ^ Bagrov, AY; Fedorova, OV; Dmitrieva, RI; et al. (1998). "Bufodienolide nature of endogenous inhibitor of Na/K ATPase in the urine from patients with acute myocardial infarction". Hypertension. 31: 1097–1103.
  3. ^ Kolmakova, EV; Haller, ST; Kennedy, DJ; et al. (2011). "Endogenous cardiotonic steroids in chronic renal failure". Nephrology, Dialysis and Transplantation. 26: 2912–2919. doi:10.1093/ndt/gfq772.
  4. ^ Fridman, AI; Matveev, SA; Agalakova, NI; et al. (2002). "Marinobufagenin, an endogenous ligand of alpha-1 Na/K-ATPase, is a marker of congestive heart failure severity". Journal of Hypertension. 20: 1189–1194.
  5. ^ Nikitina, ER; Mikhailov, AV; Nikandrova, ES; et al. (2011). "In preeclampsia endogenous cardiotonic steroids induce vascular fibrosis and impair relaxation of umbilical arteries". Journal of Hypertension. 29: 769–776. doi:10.1097/HJH.0b013e32834436a7.
  6. ^ Bagrov, AY; Shapiro, JI; Fedorova, OV (2009). "Endogenous cardiotonic steroids: physiology, pharmacology and novel therapeutic targets". Pharmacology Review. 61: 9–38. doi:10.1124/pr.108.000711.
  7. ^ Fedorova, OV; Zernetkina, VI; Shilova, VY; et al. (2015). "Synthesis of an endogenous steroidal Na pump inhibitor marinobufagenin, implicated in human cardiovascular diseases, is initiated by CYP27A1 via bile acid pathway". Circulation: Cardiovascular Genetics. 8 (5): 736–745. doi:10.1161/CIRCGENETICS.115.001217.
  8. ^ Fedorova, OV; Shilova, VY; Marshall, CA; et al. (2023). "Silencing of PKG1 gene sensitizes vascular smooth muscle cells to pro-fibrotic effect of marinobufagenin and mimics effect of aging". Journal of the American Heart Association 20. 12 (12). doi:10.1161/JAHA.122.028768. PMID 37301747.
  9. ^ Kennedy DJ, Vetteth S, Periyasamy SM, Kanj M, Fedorova L, Khouri S, Kahaleh B, Xie Z, Malhotra D, Kolodkin NI, Lakatta EG, Fedorova OV, Bagrov AY, Shapiro JI. (2006) Central role for the cardiotonic steroid, marinobufagenin, in the pathogenesis of experimental uremic cardiomyopathy. Hypertension 47: 488-495.
  10. ^ Fedorova OV, Emelianov IV, Bagrov KA, Grigorova YN, Wei W, Juhasz O, Frolova EV, Marshall CA, Lakatta EG, Konradi AO, Bagrov AY. (2015) Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists. J Hypertens 33(8):1602-1610.
  11. ^ Agalakova NI, Mikhailova EM, Ershov IA, Nadei OV, Galagudza MM, Adair CD, Romanova IV, Bagrov AY. (2024) Antibody to marinobufagenin reverses vascular fibrosis and restores vasorelaxation in chronic renal failure in rats. Int J Mol Sci Int. J. Mol. Sci. 25, 8896. https://doi.org/10.3390/ijms25168896.


 

This toxicology-related article is a stub. You can help Wikipedia by expanding it.

 

This biochemistry article is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Marinobufagenin&oldid=1269192265"