Marinobufagenin

Last updated
Marinobufagenin
Marinobufagin.svg
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
PubChem CID
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 X mark.svgN
    Key: JMNQTHQLNRILMH-OBBGIPBRSA-N X mark.svgN
  • 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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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]

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

  1. 1 2 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. PMID   8770130.
  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 (5): 1097–1103. doi:10.1161/01.HYP.31.5.1097. PMID   9576120.
  3. ↑ Kolmakova, EV; Haller, ST; Kennedy, DJ; et al. (2011). "Endogenous cardiotonic steroids in chronic renal failure". Nephrology, Dialysis and Transplantation. 26 (9): 2912–2919. doi:10.1093/ndt/gfq772. PMC   3203407 . PMID   21292813.
  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 (6): 1189–1194. doi:10.1097/00004872-200206000-00032. PMID   12023690.
  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 (4): 769–776. doi:10.1097/HJH.0b013e32834436a7. PMC   3053428 . PMID   21330936.
  6. ↑ Bagrov, AY; Shapiro, JI; Fedorova, OV (2009). "Endogenous cardiotonic steroids: physiology, pharmacology and novel therapeutic targets". Pharmacological Reviews. 61 (1): 9–38. doi:10.1124/pr.108.000711. PMC   2763610 . PMID   19325075.
  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. PMC   4618091 . PMID   26374826.
  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. 12 (12) e028768. doi:10.1161/JAHA.122.028768. PMC   10356040 . PMID   37301747.
  9. ↑ Kennedy, David J.; Vetteth, Sandeep; Periyasamy, Sankaridrug M.; Kanj, Mohamed; Fedorova, Larisa; Khouri, Samer; Kahaleh, M. Bashar; Xie, Zijian; Malhotra, Deepak; Kolodkin, Nikolai I.; Lakatta, Edward G.; Fedorova, Olga V.; Bagrov, Alexei Y.; Shapiro, Joseph I. (2006). "Central Role for the Cardiotonic Steroid Marinobufagenin in the Pathogenesis of Experimental Uremic Cardiomyopathy". Hypertension. 47 (3): 488–495. doi:10.1161/01.hyp.0000202594.82271.92. PMID   16446397.
  10. ↑ Fedorova, Olga V.; Emelianov, Igor V.; Bagrov, Konstantin A.; Grigorova, Yulia N.; Wei, Wen; Juhasz, Ondrej; Frolova, Elena V.; Marshall, Courtney A.; Lakatta, Edward G.; Konradi, Alexandra O.; Bagrov, Alexei Y. (2015). "Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists". Journal of Hypertension. 33 (8): 1602–1610. doi:10.1097/HJH.0000000000000591. PMC   4547457 . PMID   26136067.
  11. ↑ Agalakova, Natalia I.; Mikhailova, Elena V.; Ershov, Ivan A.; Nadei, Olga V.; Pyankov, Arseny A.; Galagoudza, Michael M.; Adair, C. David; Romanova, Irina V.; Bagrov, Alexei Y. (2024). "Antibody to Endogenous Cardiotonic Steroid Reverses Vascular Fibrosis and Restores Vasorelaxation in Chronic Kidney Disease". International Journal of Molecular Sciences. 25 (16): 8896. doi: 10.3390/ijms25168896 . PMC   11354990 . PMID   39201581.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.