Examination of the cellular mechanisms by which marinobufagenin inhibits cytotrophoblast function

The Journal of Biological Chemistry
Mohammad N UddinJules Puschett

Abstract

Marinobufagenin (MBG) is an endogenous mammalian cardiotonic steroid involved in the inhibition of Na(+)/K(+)-ATPase. Increased plasma levels have been reported in patients with volume expansion-related hypertension. We have recently demonstrated that MBG impairs first trimester cytotrophoblast (CTB) cell proliferation, migration, and invasion, which may play a role in the development of preeclampsia. However, whether apoptosis contributes to altered CTB cell function by MBG remains unknown. Using the human extravillous CTB cell line SGHPL-4, we examined the effect of MBG and a similar Na(+)/K(+)-ATPase inhibitor, ouabain, on the phosphorylation status of Jnk, p38, and Src. Additionally, we measured apoptosis by caspase 9 and 3/7 activity and by annexin-V staining. We also investigated interleukin-6 (IL-6) secretion with or without p38 and Jnk inhibition. MBG significantly increased the phosphorylation of Jnk, p38, and Src and increased the expression of caspase 9 and 3/7 indicating the activation of apoptosis. MBG treatment also stimulated the expression of the early apoptosis marker, annexin-V, which was prevented by Jnk and p38 inhibition. MBG also stimulated the secretion of IL-6, which was attenuated by p38 inhibition. Oua...Continue Reading

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Citations

Mar 28, 2009·Pharmacological Reviews·Alexei Y BagrovOlga V Fedorova
Apr 24, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Mohammad N UddinJules B Puschett
Feb 6, 2009·American Journal of Nephrology·Mohammad N UddinJules B Puschett
Jun 1, 2012·Reproductive Sciences·Valentina V Ishkaraeva-YakovlevaAlexei Y Bagrov
Jan 30, 2009·American Journal of Physiology. Renal Physiology·Larisa V FedorovaDeepak Malhotra
Aug 29, 2014·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Mohammad N UddinThomas J Kuehl
Jul 23, 2014·International Journal of Environmental Research and Public Health·Darijana HorvatMohammad Nasir Uddin
Jun 12, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Mohammad N UddinThomas J Kuehl
Mar 2, 2016·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Chase CawyerM Nasir Uddin
Apr 27, 2010·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Jules B PuschettMohammad N Uddin
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May 6, 2014·American Journal of Obstetrics and Gynecology·Chase R CawyerMohammad N Uddin
Dec 23, 2010·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Mohammad Nasir UddinJules B Puschett
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Sep 21, 2010·Biochimica Et Biophysica Acta·Mohammad N UddinJules B Puschett
Dec 4, 2014·Translational Research : the Journal of Laboratory and Clinical Medicine·Saunders LinMohammad N Uddin
Jul 24, 2013·American Journal of Hypertension·Irina E ZazerskayaAlexei Y Bagrov
May 12, 2017·International Journal of Environmental Research and Public Health·Ahmed F PanthoMohammad Nasir Uddin
Oct 5, 2016·Molecular and Cellular Biochemistry·Syeda H AfrozeM Nasir Uddin
Oct 27, 2020·Frontiers in Physiology·Sergej PirkmajerAlexander V Chibalin
Apr 19, 2021·Molecular and Cellular Biochemistry·Darijana HorvatMohammad Nasir Uddin

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